[go: up one dir, main page]

EP2205968B1 - Dispositifs modulaires à utiliser sur place et leurs utilisations - Google Patents

Dispositifs modulaires à utiliser sur place et leurs utilisations Download PDF

Info

Publication number
EP2205968B1
EP2205968B1 EP08836072.2A EP08836072A EP2205968B1 EP 2205968 B1 EP2205968 B1 EP 2205968B1 EP 08836072 A EP08836072 A EP 08836072A EP 2205968 B1 EP2205968 B1 EP 2205968B1
Authority
EP
European Patent Office
Prior art keywords
sample
assay
analyte
individual
bodily fluid
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
EP08836072.2A
Other languages
German (de)
English (en)
Other versions
EP2205968A4 (fr
EP2205968A1 (fr
Inventor
Tammy Burd
Ian Gibbons
Elizabeth A. Holmes
Gary Frenzel
Anthony Joseph Nugent
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Theranos Inc
Original Assignee
Theranos Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=40509067&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=EP2205968(B1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Priority to EP17155280.5A priority Critical patent/EP3181228B1/fr
Priority to DK13178059.5T priority patent/DK2657699T3/en
Priority to EP20187805.5A priority patent/EP3756767B1/fr
Priority to EP24172878.1A priority patent/EP4450163A3/fr
Priority to EP13178059.5A priority patent/EP2657699B1/fr
Application filed by Theranos Inc filed Critical Theranos Inc
Publication of EP2205968A1 publication Critical patent/EP2205968A1/fr
Publication of EP2205968A4 publication Critical patent/EP2205968A4/fr
Publication of EP2205968B1 publication Critical patent/EP2205968B1/fr
Application granted granted Critical
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/5302—Apparatus specially adapted for immunological test procedures
    • G01N33/5304—Reaction vessels, e.g. agglutination plates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/15—Devices for taking samples of blood
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/15—Devices for taking samples of blood
    • A61B5/150007—Details
    • A61B5/150755—Blood sample preparation for further analysis, e.g. by separating blood components or by mixing
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/15—Devices for taking samples of blood
    • A61B5/151—Devices specially adapted for taking samples of capillary blood, e.g. by lancets, needles or blades
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J19/0046—Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/02—Burettes; Pipettes
    • B01L3/0241—Drop counters; Drop formers
    • B01L3/0262—Drop counters; Drop formers using touch-off at substrate or container
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5025—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures for parallel transport of multiple samples
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/52—Containers specially adapted for storing or dispensing a reagent
    • B01L3/527—Containers specially adapted for storing or dispensing a reagent for a plurality of reagents
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L7/00—Heating or cooling apparatus; Heat insulating devices
    • B01L7/52—Heating or cooling apparatus; Heat insulating devices with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L9/00—Supporting devices; Holding devices
    • B01L9/54—Supports specially adapted for pipettes and burettes
    • B01L9/543—Supports specially adapted for pipettes and burettes for disposable pipette tips, e.g. racks or cassettes
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M1/00—Apparatus for enzymology or microbiology
    • C12M1/02—Apparatus for enzymology or microbiology with agitation means; with heat exchange means
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M1/00—Apparatus for enzymology or microbiology
    • C12M1/26—Inoculator or sampler
    • C12M1/266—Magnetic separators
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00—Sampling; Preparing specimens for investigation
    • G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
    • G01N1/38—Diluting, dispersing or mixing samples
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
    • G01N33/5091—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing the pathological state of an organism
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/5302—Apparatus specially adapted for immunological test procedures
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • G01N33/54313—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals the carrier being characterised by its particulate form
    • G01N33/54326—Magnetic particles
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • G01N33/54366—Apparatus specially adapted for solid-phase testing
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • G01N33/54366—Apparatus specially adapted for solid-phase testing
    • G01N33/54386—Analytical elements
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/569—Immunoassay; Biospecific binding assay; Materials therefor for microorganisms, e.g. protozoa, bacteria, viruses
    • G01N33/56966—Animal cells
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
    • G01N33/57484—Immunoassay; Biospecific binding assay; Materials therefor for cancer involving compounds serving as markers for tumor, cancer, neoplasia, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides, metabolites
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G01N33/6803—General methods of protein analysis not limited to specific proteins or families of proteins
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/94—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving narcotics or drugs or pharmaceuticals, neurotransmitters or associated receptors
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/00584—Control arrangements for automatic analysers
    • G01N35/00722—Communications; Identification
    • G01N35/00732—Identification of carriers, materials or components in automatic analysers
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/00584—Control arrangements for automatic analysers
    • G01N35/00722—Communications; Identification
    • G01N35/00871—Communications between instruments or with remote terminals
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/02—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/02—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations
    • G01N35/028—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations having reaction cells in the form of microtitration plates
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/08—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a stream of discrete samples flowing along a tube system, e.g. flow injection analysis
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N35/1065—Multiple transfer devices
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N35/1065—Multiple transfer devices
    • G01N35/1074—Multiple transfer devices arranged in a two-dimensional array
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N37/00—Details not covered by any other group of this subclass
    • G—PHYSICS
    • G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16H—HEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA
    • G16H10/00—ICT specially adapted for the handling or processing of patient-related medical or healthcare data
    • G16H10/40—ICT specially adapted for the handling or processing of patient-related medical or healthcare data for data related to laboratory analysis, e.g. patient specimen analysis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B10/00—Instruments for taking body samples for diagnostic purposes; Other methods or instruments for diagnosis, e.g. for vaccination diagnosis, sex determination or ovulation-period determination; Throat striking implements
    • A61B10/0038—Devices for taking faeces samples; Faecal examination devices
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B10/00—Instruments for taking body samples for diagnostic purposes; Other methods or instruments for diagnosis, e.g. for vaccination diagnosis, sex determination or ovulation-period determination; Throat striking implements
    • A61B10/0045—Devices for taking samples of body liquids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B10/00—Instruments for taking body samples for diagnostic purposes; Other methods or instruments for diagnosis, e.g. for vaccination diagnosis, sex determination or ovulation-period determination; Throat striking implements
    • A61B10/0045—Devices for taking samples of body liquids
    • A61B10/0051—Devices for taking samples of body liquids for taking saliva or sputum samples
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B10/00—Instruments for taking body samples for diagnostic purposes; Other methods or instruments for diagnosis, e.g. for vaccination diagnosis, sex determination or ovulation-period determination; Throat striking implements
    • A61B10/0045—Devices for taking samples of body liquids
    • A61B10/0058—Devices for taking samples of body liquids for taking sperm samples
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B10/00—Instruments for taking body samples for diagnostic purposes; Other methods or instruments for diagnosis, e.g. for vaccination diagnosis, sex determination or ovulation-period determination; Throat striking implements
    • A61B10/0045—Devices for taking samples of body liquids
    • A61B10/007—Devices for taking samples of body liquids for taking urine samples
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B10/00—Instruments for taking body samples for diagnostic purposes; Other methods or instruments for diagnosis, e.g. for vaccination diagnosis, sex determination or ovulation-period determination; Throat striking implements
    • A61B10/02—Instruments for taking cell samples or for biopsy
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B10/00—Instruments for taking body samples for diagnostic purposes; Other methods or instruments for diagnosis, e.g. for vaccination diagnosis, sex determination or ovulation-period determination; Throat striking implements
    • A61B10/0045—Devices for taking samples of body liquids
    • A61B2010/0074—Vaginal or cervical secretions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B10/00—Instruments for taking body samples for diagnostic purposes; Other methods or instruments for diagnosis, e.g. for vaccination diagnosis, sex determination or ovulation-period determination; Throat striking implements
    • A61B10/0045—Devices for taking samples of body liquids
    • A61B2010/0077—Cerebrospinal fluid
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277—Apparatus
    • B01J2219/00279—Features relating to reactor vessels
    • B01J2219/00281—Individual reactor vessels
    • B01J2219/00283—Reactor vessels with top opening
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277—Apparatus
    • B01J2219/00279—Features relating to reactor vessels
    • B01J2219/00281—Individual reactor vessels
    • B01J2219/00286—Reactor vessels with top and bottom openings
    • B01J2219/00292—Reactor vessels with top and bottom openings in the shape of pipette tips
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277—Apparatus
    • B01J2219/00279—Features relating to reactor vessels
    • B01J2219/00306—Reactor vessels in a multiple arrangement
    • B01J2219/00313—Reactor vessels in a multiple arrangement the reactor vessels being formed by arrays of wells in blocks
    • B01J2219/00315—Microtiter plates
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277—Apparatus
    • B01J2219/00351—Means for dispensing and evacuation of reagents
    • B01J2219/00364—Pipettes
    • B01J2219/00367—Pipettes capillary
    • B01J2219/00369—Pipettes capillary in multiple or parallel arrangements
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277—Apparatus
    • B01J2219/00351—Means for dispensing and evacuation of reagents
    • B01J2219/00364—Pipettes
    • B01J2219/00371—Pipettes comprising electrodes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277—Apparatus
    • B01J2219/00351—Means for dispensing and evacuation of reagents
    • B01J2219/00385—Printing
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277—Apparatus
    • B01J2219/00457—Dispensing or evacuation of the solid phase support
    • B01J2219/00459—Beads
    • B01J2219/00466—Beads in a slurry
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277—Apparatus
    • B01J2219/00495—Means for heating or cooling the reaction vessels
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277—Apparatus
    • B01J2219/00497—Features relating to the solid phase supports
    • B01J2219/005—Beads
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/0068—Means for controlling the apparatus of the process
    • B01J2219/00693—Means for quality control
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/0068—Means for controlling the apparatus of the process
    • B01J2219/00702—Processes involving means for analysing and characterising the products
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/04—Exchange or ejection of cartridges, containers or reservoirs
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/06—Fluid handling related problems
    • B01L2200/0689—Sealing
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/14—Process control and prevention of errors
    • B01L2200/141—Preventing contamination, tampering
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/14—Process control and prevention of errors
    • B01L2200/148—Specific details about calibrations
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/06—Auxiliary integrated devices, integrated components
    • B01L2300/0627—Sensor or part of a sensor is integrated
    • B01L2300/0654—Lenses; Optical fibres
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0809—Geometry, shape and general structure rectangular shaped
    • B01L2300/0829—Multi-well plates; Microtitration plates
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/18—Means for temperature control
    • B01L2300/1805—Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/043—Moving fluids with specific forces or mechanical means specific forces magnetic forces
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/02—Burettes; Pipettes
    • B01L3/021—Pipettes, i.e. with only one conduit for withdrawing and redistributing liquids
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/02—Burettes; Pipettes
    • B01L3/0275—Interchangeable or disposable dispensing tips
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L7/00—Heating or cooling apparatus; Heat insulating devices
    • B01L7/52—Heating or cooling apparatus; Heat insulating devices with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples
    • B01L7/525—Heating or cooling apparatus; Heat insulating devices with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples with physical movement of samples between temperature zones
    • B01L7/5255—Heating or cooling apparatus; Heat insulating devices with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples with physical movement of samples between temperature zones by moving sample containers
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N2035/00178—Special arrangements of analysers
    • G01N2035/00237—Handling microquantities of analyte, e.g. microvalves, capillary networks
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/00584—Control arrangements for automatic analysers
    • G01N35/00722—Communications; Identification
    • G01N35/00732—Identification of carriers, materials or components in automatic analysers
    • G01N2035/00821—Identification of carriers, materials or components in automatic analysers nature of coded information
    • G01N2035/00851—Identification of carriers, materials or components in automatic analysers nature of coded information process control parameters
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/00584—Control arrangements for automatic analysers
    • G01N35/00722—Communications; Identification
    • G01N35/00871—Communications between instruments or with remote terminals
    • G01N2035/00881—Communications between instruments or with remote terminals network configurations
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/00584—Control arrangements for automatic analysers
    • G01N2035/0097—Control arrangements for automatic analysers monitoring reactions as a function of time
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N2035/1027—General features of the devices
    • G01N2035/103—General features of the devices using disposable tips
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N2035/1027—General features of the devices
    • G01N2035/1032—Dilution or aliquotting
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N2035/1027—General features of the devices
    • G01N2035/1034—Transferring microquantities of liquid
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N2035/1027—General features of the devices
    • G01N2035/1048—General features of the devices using the transfer device for another function
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
    • G01N2333/46—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans from vertebrates
    • G01N2333/47—Assays involving proteins of known structure or function as defined in the subgroups
    • G01N2333/4701—Details
    • G01N2333/4737—C-reactive protein
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
    • G01N2333/475—Assays involving growth factors
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
    • G01N2333/705—Assays involving receptors, cell surface antigens or cell surface determinants
    • G01N2333/71—Assays involving receptors, cell surface antigens or cell surface determinants for growth factors; for growth regulators
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/90—Enzymes; Proenzymes
    • G01N2333/91—Transferases (2.)
    • G01N2333/912—Transferases (2.) transferring phosphorus containing groups, e.g. kinases (2.7)
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/90—Enzymes; Proenzymes
    • G01N2333/91—Transferases (2.)
    • G01N2333/912—Transferases (2.) transferring phosphorus containing groups, e.g. kinases (2.7)
    • G01N2333/91205—Phosphotransferases in general
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/90—Enzymes; Proenzymes
    • G01N2333/91—Transferases (2.)
    • G01N2333/912—Transferases (2.) transferring phosphorus containing groups, e.g. kinases (2.7)
    • G01N2333/91205—Phosphotransferases in general
    • G01N2333/9129—Transferases for other substituted phosphate groups (2.7.8)
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00—Detection or diagnosis of diseases
    • G01N2800/26—Infectious diseases, e.g. generalised sepsis
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00—Detection or diagnosis of diseases
    • G01N2800/60—Complex ways of combining multiple protein biomarkers for diagnosis
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T29/00—Metal working
    • Y10T29/49—Method of mechanical manufacture
    • Y10T29/49826—Assembling or joining
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T436/00—Chemistry: analytical and immunological testing
    • Y10T436/25—Chemistry: analytical and immunological testing including sample preparation
    • Y10T436/25375—Liberation or purification of sample or separation of material from a sample [e.g., filtering, centrifuging, etc.]

Definitions

  • Point-of-care systems can rapidly deliver test results to medical personnel, other medical professionals and patients. Early diagnosis of a disease or disease progression can allow medical personnel to begin or modify therapy in a timely manner.
  • Multiplexed biomarker measurement can provide additional knowledge of the condition of a patient. For example, when monitoring the effects of a drug, three or more biomarkers can be measured in parallel.
  • microtiter plates and other similar apparatuses have been used to perform multiplexed separation-based assays.
  • a microtiter plate (for example, a 384 well microtiter plate) can perform a large number of assays in parallel.
  • POC Point-of-Care
  • the number of assays that can be performed in parallel is often limited by the size of the device and the volume of the sample to be analyzed. In many POC devices, the number assays performed is about 2 to 10. A POC device capable of performing multiplexed assays on a small sample would be desirable.
  • a shortcoming of many multiplexed POC assay devices is the high cost of manufacturing the components of the device. If the device is disposable, the high cost of the components can make the manufacturing of a POC device impractical. Further, for multiplexed POC devices that incorporate all of the necessary reagents onboard of the device, if any one of those reagents exhibit instability, an entire manufactured lot of devices may have to be discarded even if all the other reagents are still usable.
  • a multiplexed POC assay suitable to each customer can be very expensive, difficult to calibrate, and difficult to maintain quality control.
  • POC methods have proven to be very valuable in monitoring disease and therapy (for example, blood glucose systems in diabetes therapy, Prothrombin Time measurement in anticoagulant therapy using Warfarin). By measuring multiple markers, it is believed that complex diseases (such as cancer) and therapies such as multi-drug therapy for cancer can be better monitored and controlled.
  • WO 2007/002579 discloses devices and methods for point of care instruments. Gibbons I et al., Clin. Chem., 35/9, 1869-1873, September 1989 discusses a patient-side immunoassay system with a single-use cartridge for measuring analytes in blood. US 2007/224084 discloses portable medical devices that allow real-time detection of analytes from a biological fluid and which are useful for providing point-of-care testing for a variety of medical applications.
  • a desirable design provides modular capture surfaces and assay incubation elements. Furthermore, modular capture surfaces and assay incubation elements need to be integrated into POC disposables suited for just-in-time (JIT) manufacturing methods. It would be desirable to provide a customizable POC device at a practical cost to user and the manufacturer. The present invention addresses these needs and provides related advantages as well.
  • a cartridge for automated detection of an analyte in a bodily fluid sample comprising: an array of addressable assay units configured to run a chemical reaction that yields a detectable signal indicative of the presence or absence of the analyte; and an array of addressable reagent units, wherein an individual addressable reagent unit of the array is addressed to correspond to an individual addressable assay unit of the array of assay units, and wherein the individual reagent unit is configured to be calibrated in reference to the corresponding individual assay unit before the arrays are assembled on the cartridge and wherein the individual assay unit of the array of addressable assay units and the individual reagent unit of the array of addressable reagent units are configured to be movable into fluid communication such that reagents for running the chemical reaction are brought to contact with the portion of the sample in the assay unit.
  • the device can further comprise a sample collection unit configured to receive the bodily fluid sample.
  • a cartridge for automated detection of an analyte in a bodily fluid sample comprising: a sample collection unit configured to receive the bodily fluid sample; an array of assay units configured to receive a portion of the sample from the sample collection unit and run a chemical reaction that yields a detectable signal indicative of the presence of the analyte in the sample; and an array of reagent units containing reagents for running the chemical reaction; wherein an individual assay unit of the array of assay units and an individual reagent unit of the array of reagents units are configured to be movable into fluid communication such that reagents for running the chemical reaction are brought to contact with the bodily fluid sample in the assay unit.
  • An individual reagent unit can be configured to receive a movable assay unit.
  • the individual assay unit comprises an assay tip.
  • the individual assay unit is configured to run an immunoassay.
  • the bodily fluid sample can be a blood sample.
  • a sample collection unit is configured to receive a volume of the bodily fluid sample about 50, 20, 10, 5 or 3 microliters or less. In an instance, the sample collection unit is configured to receive a volume of the bodily fluid sample equivalent to a single drop of blood.
  • a cartridge as described herein can comprise a pretreatment unit configured to retrieve a portion of the bodily fluid sample for running the chemical reaction to detect the analyte and the pretreatment unit can be configured to retrieve plasma from whole blood sample received in the sample collection unit.
  • a system for automated detection of an analyte in a bodily fluid sample comprising: a cartridge as described herein; and a detection assembly for detecting the detectable signal indicative of the presence or absence of the analyte.
  • the system can further comprise a programmable mechanical device configured to move the individual assay unit from a first location to a second location.
  • a system comprises a fluid transfer device.
  • the fluid transfer device can be a pipette and can be automated.
  • a system can also comprise a communication assembly for transmitting a protocol based on the analyte to be detected.
  • a system herein comprises a heating block configured to receive an individual assay unit and can also comprise a magnetic block, for example, that can be used for separation of red cells from the sample.
  • a system for automated detection of a plurality of analytes in a bodily fluid sample, comprising: a fluidic device comprising: a sample collection unit configured to contain the bodily fluid sample; an array of assay units, wherein an individual assay unit of said array of assay units is configured to run a chemical reaction that yields a signal indicative of an individual analyte of said plurality of analytes being detected; and an array of reagent units, wherein an individual reagent unit of said array of reagent units contains a reagent; and a fluid transfer device comprising a plurality of heads, wherein an individual head of the plurality of heads is configured to engage the individual assay unit, and wherein said fluid transfer device comprises a programmable processor configured to direct fluid transfer of the bodily fluid sample from the sample collection unit and the reagent from the individual reagent unit into the individual assay unit.
  • the configuration of the processor to direct fluid transfer effects a degree of dilution of the bodily fluid sample in the array of assay units to bring signals indicative of the plurality of analytes being detected within a detectable range, such that said plurality of analytes are detectable with said system.
  • a bodily fluid sample comprises at least two analytes that are present at concentrations that differ by at least 2, 5, 10, 15, 50, or 100 orders of magnitude.
  • the degree of dilution of the bodily fluid sample can bring the signals indicative of the at least two analytes within the detectable range.
  • a system herein can further comprise a detector configured to detect signal intensities of the detectable range.
  • An exemplary detector is a photomultiplier and a detectable range of the detector can be about 20 to about 10 million counts.
  • the individual head of a fluid transfer device is configured to adhere to the individual assay unit.
  • the individual assay unit can provide an immunoassay reaction site.
  • the individual assay unit is a pipette tip.
  • the fluid transfer device can be a pipette such as an air-displacement pipette.
  • the fluid transfer device can also comprises a motor in communication with the programmable processor, wherein the motor can move said plurality of heads based on a protocol from said programmable processor.
  • a system for automated detection of a plurality of analytes in a plasma portion of a whole blood sample, comprising: a device configured to automatically receive and process the whole blood sample to yield the plasma portion, from which a detectable signal indicative of the presence or absence of the analyte of interest is generated onboard the device; and a detection assembly for detecting the detectable signal indicative of the presence or absence of the analyte.
  • a method of detecting an analyte in a bodily fluid sample comprising: providing a bodily fluid sample to a cartridge as described herein; allowing said sample to react within at least one assay unit; and detecting said detectable signal generated from said analyte collected in said sample of bodily fluid.
  • the bodily fluid sample can be blood and the method can comprise retrieving plasma from the blood.
  • a method of on-demand assembly of a cartridge for automated detection of an analyte in a bodily fluid sample wherein the cartridge comprises a housing, said housing comprising: an array of addressable assay units, wherein an individual assay unit of the array is configured to run a chemical reaction that yields a detectable signal indicative of the presence or absence of the analyte; and an array of addressable reagent units, wherein an individual reagent unit of the array is addressed to correspond to the individual assay unit
  • said method comprises: (i) placing according to the analyte to be detected an array of addressable assay units, wherein an individual assay unit of the array is configured to run a chemical reaction that detects an analyte of interest ordered by said end user, into the housing; (ii) placing according to the analyte to be detected an array of reagent units, wherein an individual reagent unit of the array corresponds to the individual assay unit, into the housing; and (iii)
  • the method can comprise selecting an analyte to be detected.
  • the method comprises sealing the cartridge.
  • the method comprises labeling the cartridge with a readable label indicating the analyte to be detected, for example with a bar code or RFID.
  • a method for automated detection of a plurality of analytes in a bodily fluid sample comprising: providing the bodily fluid sample to a fluidic device, wherein the fluidic device comprises: a sample collection unit configured to contain the bodily fluid sample; an array of assay units, wherein an individual assay unit of said array of assay units is configured to run a chemical reaction that yields a signal indicative of an individual analyte of said plurality of analytes being detected; and an array of reagent units, wherein an individual reagent unit of said array of reagent units contains a reagent; engaging the individual assay unit using a fluid transfer device; transferring the bodily fluid sample from the sample collection unit to the individual assay unit using the fluid transfer device; and transferring the reagent from the individual reagent unit to the individual assay unit, thereby reacting the reagent with the bodily fluid sample to yield the signal indicative of the individual analyte of the plurality of analytes being detected.
  • the fluid transfer device comprises a plurality of heads, wherein an individual head of the plurality of heads is configured to engage the individual assay unit; and wherein said fluid transfer device comprises a programmable processor configured to direct fluid transfer of the bodily fluid sample from the sample collection unit and the reagent from the individual reagent unit into the individual assay unit.
  • the method can further comprise providing instructions to the programmable processor, wherein the instructions can direct the step of transferring the bodily fluid sample to the individual assay unit.
  • the step of transferring the bodily fluid sample effects a degree of dilution of the bodily fluid sample in the individual assay unit to bring the signal indicative the individual analyte of the plurality of analytes being detected within a detectable range.
  • the bodily fluid sample can comprise at least two individual analytes that are present at concentrations that differ by at least 2, 5, 10, 15, 50, or 100 orders of magnitude.
  • the degree of dilution of the bodily fluid sample brings the signals indicative of the at least two individual analytes within the detectable range.
  • the detectable range is about 1000 to about 1 million counts per second using a photomultiplier.
  • the reagent in the individual reagent unit is an enzyme substrate for an immunoassay and the method can further comprise repeating the step of transferring the reagent from the individual reagent unit after the reaction to yield the signal indicative of the individual analyte of the plurality of analytes being detected is complete, thereby creating a second reaction to yield a second signal indicative of the individual analyte.
  • An intensity of the signal and a second intensity of the second signal indicative of the individual analyte can be averaged to calculate the final intensity of the signal indicative of the individual analyte.
  • a method is described herein of measuring a volume of a liquid sample, comprising: reacting a known quantity of a control analyte in a liquid sample with a reagent to yield a detectable signal indicative of the control analyte; and comparing said detectable signal with an expected detectable signal, wherein the expected signal is indicative of an expected volume of the liquid sample, and wherein said comparison provides a measurement of said volume of said liquid sample being measured.
  • the control analyte is not normally present in said liquid sample in a detectable amount.
  • the method can comprise verifying the volume of said liquid sample when the measurement of the volume of the sample is within about 50% of the expect volume of the liquid sample.
  • the method further comprises: reacting a bodily fluid sample containing a target analyte with a reagent to yield a detectable signal indicative of the target analyte; and measuring the quantity of the target analyte in the bodily fluid sample using an intensity of said detectable signal indicative of the target analyte and the measurement of said volume of said liquid sample.
  • the liquid sample and the bodily fluid sample can be the same sample and the control analyte does not react with the target analyte in the bodily fluid sample. In some instances, the liquid sample and the bodily fluid sample are different liquid samples.
  • the control analyte can be, for example, fluorescein-labeled albumin, fluorescein labeled IgG, anti-fluorescein, anti-digoxigenin, digoxigenin-labeled albumin, digoxigenin-labeled IgG, biotinylated proteins, non-human IgG.
  • a method of retrieving plasma from a blood sample comprises: mixing a blood sample in the presence of magnetizable particles in a sample collection unit, wherein the magnetizable particles comprise an antibody capture surface for binding to non-plasma portions of the blood sample; and applying a magnetic field above a plasma collection area to the mixed blood sample to effect suspension of the non-plasma portions of the blood sample on top of the plasma collection area.
  • the sample collection unit is a capillary tube.
  • the blood sample can be less than about 20 microliters and the plasma retrieved can be less than about 10 microliters.
  • the blood sample is not diluted.
  • mixing occurs in the presence of antibodies unbound to a solid surface.
  • the mixing can comprise mixing by syringe action.
  • Also described is a method of using automated immunoassay for detecting an analyte present in plasma portion of a whole blood sample comprising: providing a whole blood sample to a device that is configured to automatically receive and process on board the whole blood sample to yield the plasma portion, from which a detectable signal indicative of the presence or absence of the analyte of interest is generated on board; detecting said signal that is indicative of the presence or absence of the analyte in said bodily fluid sample; and transmitting result of (b) to an end user.
  • the immunoassay can be an ELISA. In some instances, the result is transmitted wirelessly.
  • a method as described herein is carried out in a system as described herein.
  • Figure 1 illustrates an exemplary device of the invention comprising assay units, reagents unit, and other modular components of the device.
  • Figure 2 illustrates two side-cut away views of the exemplary device of Figure 1 comprising cavities in the housing of the device shaped to accommodate an assay unit, a reagent unit, and a sample tip.
  • Figure 3A demonstrates an exemplary assay unit that comprises a small tip or tubular formation.
  • Figure 3B demonstrates an example of a sample tip as described herein.
  • Figures 4A and 4B illustrate two examples of a reagent unit comprising a cup.
  • Figure 5 demonstrates an example of a system comprising a device and a fluid transfer device.
  • Figure 6 illustrates an exemplary system of the invention comprising a heating block for temperature control and a detector.
  • Figure 7 demonstrates an exemplary a system wherein a patient delivers blood to a device and then the device is inserted into a reader.
  • Figure 8 illustrates the process flow of building a system for assessing the medical condition of a patient.
  • Figures 9A through 9E demonstrate an example of a plasma separation method wherein a whole blood sample has been aspirated into a sample tip and a magnetic reagent is mixed and suspended with the sample, then a magnetic field is applied to the whole blood sample and magnetic reagent mixture. Separated blood plasma sample can then be distributed into a well of a device.
  • Figure 10 demonstrates an exemplary method of a control assay as described herein comprising a known quantity of control analyte.
  • Figure 11 illustrates a thin film, for example, contamination, within the tip when a liquid is expelled and another liquid aspirated.
  • Figure 12 illustrates a calibration curve correlating an assay unit and a reagent unit for conducting an assay for VEGFR2.
  • Figure 13 illustrates a calibration curve correlating results for an assay unit and a reagent unit for conducting an assay for P1GF in a system, as measured with a luminometer.
  • Figure 14 illustrates CRP concentration plotted against the assay signal (photon counts) and the data fitted to a 5-term polynomial function to generate a calibration function.
  • Figure 15 shows a fit was achieved between a model and the values of the parameters Smax, C0.5 and D as described herein.
  • Figure 16 displays data according to the dilution used to achieve the final concentration in an assay tip.
  • Figure 17 illustrates the normalized assay response (B/Bmax) is plotted against the log normalized concentration (C/C0.5) for relative dilutions: 1:1 (solid line), 5:1 (dashed line), and 25:1 (dotted line).
  • Figures 18 and 19 illustrate a similar example as Figure 17 at different normalized concentrations.
  • Figure 20 demonstrates the assay response for a control analyte after the steps of: removal of the detector antibody, washing the assay, and adding a substrate, as read in a spectro-luminometer for 0.5 s.
  • Figure 21 demonstrates the results of an assay that was evaluated by measuring photons produced over about 10 s in a system herein.
  • the embodiments and aspects of the invention described herein pertain to devices, systems, and methods for automated detection of an analyte in a sample of bodily fluid.
  • the invention is capable of detecting and/or quantifying analytes that are associated with specific biological processes, physiological conditions, disorders or stages of disorders, or effects of biological or therapeutic agents.
  • a device for automated detection of an analyte in a bodily fluid sample comprises an array of addressable assay units configured to run a chemical reaction that yields a detectable signal indicative of the presence or absence of the analyte, and an array of addressable reagent units, each of which is addressed to correspond to one or more addressable assay units in said device, such that individual reagent units can be calibrated in reference to the corresponding assay unit(s) before the arrays are assembled on the device.
  • a device for automated detection of an analyte in a bodily fluid sample comprises an array of assay units configured to run a chemical reaction that yields a detectable signal indicative of the presence of the analyte, and an array of reagent units containing reagents for running the chemical reaction, wherein at least one of the assay units and at least one of the reagent units are movable relative to each other within the device such that reagents for running the chemical reaction are automatically brought to contact with the bodily fluid sample in the assay unit.
  • the array of assay units or reagent units can be addressed according to the chemical reaction to be run by the configured assay unit.
  • at least one of the assay units and at least one of the reagent units are movable relative to each other within the device such that reagents for running the chemical reaction are automatically brought to contact with the bodily fluid sample in the assay unit.
  • the device of the invention is self-contained and comprises all reagents, liquid- and solid-phase reagents, required to perform a plurality of assays in parallel.
  • the device is configured to perform at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50, 100, 200, 500, 1000 or more assays.
  • One or more control assays can also be incorporated into the device to be performed in parallel if desired.
  • the assays can be quantitative immunoassays and can be conducted in a short period of time. Other assay type can be performed with a device of the invention including, but not limited to, measurements of nucleic acid sequences and measurements of metabolytes, such as cholesterol. In some embodiments, the assay is completed in no more than one hour, preferably less than 30, 15, 10, or 5 minutes. In other embodiments, the assay is performed in less than 5 minutes.
  • the duration of assay detection can be adjusted accordingly to the type of assay that is to be carried out with a device of the invention. For example, if needed for higher sensitivity, an assay can be incubated for more than one hour or up to more than one day. In some examples, assays that require a long duration may be more practical in other POC applications, such as home use, than in a clinical POC setting.
  • any bodily fluids suspected to contain an analyte of interest can be used in conjunction with the system or devices of the invention.
  • Commonly employed bodily fluids include but are not limited to blood, serum, saliva, urine, gastric and digestive fluid, tears, stool, semen, vaginal fluid, interstitial fluids derived from tumorous tissue, and cerebrospinal fluid.
  • a bodily fluid may be drawn from a patient and provided to a device in a variety of ways, including but not limited to, lancing, injection, or pipetting.
  • the terms subject and patient are used interchangeably herein, and refer to a vertebrate, preferably a mammal, more preferably a human. Mammals include, but are not limited to, murines, simians, humans, farm animals, sport animals, and pets.
  • a lancet punctures the skin and withdraws a sample using, for example, gravity, capillary action, aspiration, or vacuum force.
  • the lancet may be part of the device, or part of a system, or a stand alone component.
  • the lancet may be activated by a variety of mechanical, electrical, electromechanical, or any other known activation mechanism or any combination of such methods.
  • a patient can simply provide a bodily fluid to the device, as for example, could occur with a saliva sample.
  • the collected fluid can be placed in the sample collection unit within the device.
  • the device comprises at least one microneedle which punctures the skin.
  • the volume of bodily fluid to be used with a device is generally less than about 500 microliters, typically between about 1 to 100 microliters. Where desired, a sample of 1 to 50 microliters, 1 to 40 microliters, 1 to 30 microliters, 1 to 10 microliters or even 1 to 3 microliters can be used for detecting an analyte using the device.
  • the volume of bodily fluid used for detecting an analyte utilizing the subject devices or systems is one drop of fluid.
  • one drop of blood from a pricked finger can provide the sample of bodily fluid to be analyzed with a device, system or method described herein.
  • a sample of bodily fluid can be collected from a subject and delivered to a device of the invention as described hereinafter.
  • the arrays of assay and reagent units are configured to be a set of mix-and-match components.
  • the assay units can comprise at least one capture surface capable of reacting with an analyte from the sample of bodily fluid.
  • the assay unit may be a tubular tip with a capture surface within the tip. Examples of tips of the invention are described herein.
  • a reagent unit typically stores liquid or solid reagents necessary for conducting an assay that detect a give analyte.
  • Each individual assay and reagent unit can be configured for assay function independently. To assemble a device, the units can be assembled in a just-in-time fashion for use in integrated cartridges.
  • the device can be modular and include components such as a housing that is generic for all assays, assay units, such as tips, and reagent units, such as a variety of frangible or instrument operable containers that encapsulate liquid reagents.
  • an assembled device is then tested to verify calibration (the relation of the system response to known analyte levels).
  • Assay devices can be assembled from a library of premanufactured and calibrated elements on demand.
  • fluidic pathways within a device can be simple and obviate any chance of trapping bubbles and providing an efficient way to wash away excess labeled reagents in reagent excess assays such as ELISAs.
  • a housing for a device of the invention can be made of polystyrene or another moldable or machinable plastic and can have defined locations to place assay units and reagent units.
  • the housing has means for blotting tips or assay units to remove excess liquid.
  • the means for blotting can be a porous membrane, such as cellulose acetate, or a piece bibulous material such as filter paper.
  • At least one of the components of the device may be constructed of polymeric materials.
  • polymeric materials include polystyrene, polycarbonate, polypropylene, polydimethysiloxanes (PDMS), polyurethane, polyvinylchloride (PVC), polysulfone, polymethylmethacrylate (PMMA), acrylonitrile-butadiene-styrene (ABS), and glass.
  • the device or the subcomponents of the device may be manufactured by variety of methods including, without limitation, stamping, injection molding, embossing, casting, blow molding, machining, welding, ultrasonic welding, and thermal bonding.
  • a device in manufactured by injection molding, thermal bonding, and ultrasonic welding can be affixed to each other by thermal bonding, ultrasonic welding, friction fitting (press fitting), adhesives or, in the case of certain substrates, for example, glass, or semi-rigid and non-rigid polymeric substrates, a natural adhesion between the two components.
  • the device 100 is also sometimes referred to herein as a cartridge 100.
  • the device 100 comprises a housing 130 with locations to accommodate assay units 121 and reagent units 103, 122, 124, 125.
  • assay units 121 occupy a center row of the housing 130 of the device 100.
  • the assay units 121 can optionally include at least one calibration unit 126.
  • the assay units 121 are similar to pipette tips and are referred to as assay tips 121 and the calibration units 126 are referred to as calibration tips 126 herein, however, the assay units 121 can be of any shape and size as are accommodated broadly by a device 100 as described herein.
  • the assay units 121 and calibration units 126 are exemplary assay units 121 and are described in more detail herein.
  • the assay units 121 in Figure 1 can comprise a capture surface and are capable, for example, of performing a chemical reaction such as nucleic acid assays and immunoassays.
  • the assay units 121 can be assembled into the housing according to instructions or the assays that a user wishes to perform on a sample.
  • the housing of the device 100 can comprise a sample collection unit 110 configured to contain a sample.
  • a sample such as a blood sample
  • a sample tip 111 (for example, a pipette tip that couples to a fluid transfer device as described in more detail herein) can occupy another portion of the housing 130 .
  • the sample tip 111 can distribute the sample to pretreatment reagent units or pretreatment units 103, 104, 105, 106, 107, or assay units 121.
  • Exemplary pretreatment units 103, 104, 105, 106, 107 include but are not limited to: mixing units 107 , diluent or dilution units 103,104, and, if the sample is a blood sample, plasma removal or retrieval units 105, 106.
  • the pretreatment units 103, 104, 105, 106, 107 can be the same type of unit or different types of units.
  • Other pretreatment units 103, 104, 105, 106, 107 as are necessary to run a chemical reaction can be incorporated into device 100 as would be obvious to one skilled in the art with knowledge of this disclosure.
  • the units 103, 104, 105, 106, 107 can contain various amounts of reagents or diluents, flexible to whatever is needed to run the assay on the current cartridge 100 .
  • the assay units 121 can be manufactured separately from the housing 130 and then inserted into the housing 130 with pick-and-place methods.
  • the assay units 121 can fit snugly into the housing 130 or can fit loosely into the housing 130 .
  • the housing 130 is manufactured such that is holds the reagent units 103, 122, 124, 125 and/or assay units 121 snugly in place, for example during shipping or manipulation a cartridge.
  • Reagents units 103, 122, 124, 125 are shown in Figure 1 that contain a conjugate reagent 122 (for example, for use with an immunoassay), a wash reagent 125 (for example, to wash said conjugate from capture surfaces), and a substrate 124 (for example, an enzyme substrate).
  • Reagent units 103, 122, 124, 125 can be manufactured and filled separately from the housing 130 and then placed into the housing 130 . In this way, a cartridge 100 can be built in a modular manner, therefore increasing the flexibility of the cartridge 100 to be used for a variety of assays.
  • Reagents in a reagent unit 103, 122, 124, 125 can be chosen according to the assay to be run. Exemplary reagents and assays are described herein.
  • a device such as the example shown in Figure 1
  • the device can comprise tip touch-off pads 112 to remove excess sample or reagent from an assay tip 121 or a sample tip 111 after fluid transfer, for example, by a system as described herein.
  • the housing 130 can also comprise units or areas 101, 102 within the device 100 for placing a used tip or unit, for example, in order to avoid cross-contamination of a sample tip 111 or assay unit 121.
  • the device 100 comprises a sample tip 111 for transferring a sample between units of the device 100.
  • the device 100 as illustrated in Figure 1 also comprises a pretreatment tip 113 for transferring a sample that has been pretreated in a unit of the device 100 to other units of a device 100 to perform a chemical reaction.
  • the sample tip 111 can be used to remove a blood sample from the sample collection unit 110 and transfer the blood sample to pretreatment units 103, 104, 105, 106, 107 as described.
  • Red cells can be removed from the blood sample in the pretreatment units 103, 104, 105, 106, 107 and the pretreatment tip 113 can then be used to collect the blood plasma from the pretreatment units 103, 104, 105, 106, 107 and transfer the blood plasma to another pretreatment unit (for example, a diluent unit) 103, 104, 105, 106, 107 and/or to at least one assay unit 121 .
  • a sample tip 111 is the sample collection unit 110 .
  • the sample collection unit 110 is similar to a well and is configured to contain a sample as received by a user.
  • Assay units 121 and reagent units 103, 122, 124, 125 as shown in Figure 1 can be addressable to indicate the location of the units on the cartridge 100 .
  • a column of the cartridge 100 as shown in Figure 1 can contain an assay unit 121 to run an assay configured to detect C-reactive protein, and the column can contain corresponding reagent units 103, 122, 124, 125 for that assay in the same column, wherein the units are addressed to correspond to each other.
  • the addresses can be entered and stored in a computer system, and the cartridge 100 can be given a label, such as a bar code.
  • the computer system can send the addresses of the units to a system, such as those described herein, to transfer the fluids and run a reaction according to the addresses entered info the computer.
  • the addresses can be part of a protocol sent to operate the system.
  • the addresses can be in any configuration and can be altered if need be to change the protocol of running an assay, which in turn can offer a change in assay protocol or steps to a user of the cartridge that has not been typically available in prior art POC devices.
  • the housing 130 and units are configured in a 6 by 8 array of units as shown in Figure 1 .
  • the layout of the units can be of any format, for example, rectangular arrays or random layouts.
  • a cartridge 100 can comprise any number of units, for example between 1 and about 500. In some embodiments, a cartridge 100 has between 5-100 units. As an example as shown in Figure 1 , the cartridge 100 has 48 units.
  • a cavity can be shaped in a housing 220 of a device to accommodate assay units (for example, assay tips) 201 in a vertical orientation (housing horizontal) with their bosses toward the top of the device 200.
  • assay units for example, assay tips
  • a cavity can also be shaped to accommodate a reagent unit 210, 212 or a sample collection unit or tip 202.
  • the sample collection unit comprises a bendable or breakable element that serves to protect a small collection tube during shipment and to hold a plunger device in place within a capillary.
  • FIG 2A Also shown in Figure 2A are two exemplary embodiments of reagent units 210, 212 as are described herein.
  • the bottom of the housing 220 can be configured to collect waste liquids, for example, wash reagents after use that are transferred back through a hole in the housing 220 to the bottom.
  • the housing 220 can comprise an absorbent pad to collect waste fluids.
  • the assay units 201 and sample units 202 can be positioned to fit through a cavity of the housing 220 of the device 200 and extend beyond an inner support structure.
  • the reagent units 210, 212 fit snugly into the housing as is shown in Figure 2 and do not extend beyond the inner support structure.
  • the housing 220 and the areas in which the assay units 201 and reagents units 210, 212 can be held and positioned may adapt a variety of patterns.
  • each tip provides for a single assay and can be paired with or corresponded to an appropriate reagent, such as required reagents for running the designated assay.
  • Some tips provide for control assay units and have known amounts of analyte bound to their capture surfaces either in the manufacturing process or during the performance of an assay.
  • the unit is configured to run a control assay for comparison.
  • the control assay unit may comprise, for example, a capture surface and analyte that are in a solid or liquid state.
  • the device holds all reagents and liquids required by the assay.
  • the reagents within the device may include a sample diluent, a detector conjugate (for example, three enzyme-labeled antibodies), a wash solution, and an enzyme substrate. Additional reagents can be provided as needed.
  • reagents can be incorporated into a device to provide for sample pretreatment.
  • pretreatment reagents include, without limitation, white cell lysis reagents, reagents for liberating analytes from binding factors in the sample, enzymes, and detergents.
  • the pretreatment reagents can also be added to a diluent contained within the device.
  • An individual reagent unit can be configured to receive a movable assay unit.
  • the individual assay unit comprises an open ended hollow cylindrical element comprising a capture surface and a reaction cuvette.
  • a cylindrical assay unit can be referred to as an assay tip herein.
  • the individual assay unit is configured to run an immunoassay.
  • An assay unit 301 that comprises a small tip or tubular formation is shown in Figure 3A .
  • the tip 301 is configured to provide an interior cylindrical capture surface 311 and a boss 321 capable of engaging with the housing of device.
  • the boss 321 and the tip 301 is configured to engage with a mechanism of moving the tip 301 such as a system as described herein or for example, a fluid transfer device.
  • An assay tip 301 as shown in Figure 3A can comprise an opening 331 at the bottom of the tip.
  • the opening 331 can be utilized for transferring fluids or reagents in and out of an assay unit 301 .
  • an assay unit 301 as described is or is similar to a pipette tip with the improvement that the assay unit 301 comprises a capture surface 311 configured to detect an analyte in a sample.
  • the tip 301 can be manufactured by an injection-molded process.
  • the tip 301 is made of a clear polystyrene for use with chemiluminescence assays.
  • an exemplary tip 301 comprises a boss (shown as the larger top half of the tip 301 ), which can engage with a housing and can engage, for example, with tapered elements of a fluid transfer device and/or pipetting devices so as to form a pressure-tight seal.
  • the exemplary tip 301 comprises a smaller cylindrical part.
  • an assay capture surface is contained within the smaller cylindrical part. The assay capture surface can be anywhere within the tip 301 or on the outside of the tip 301 .
  • the surface of the tip 301 can be of many geometries including, but not limited to, tubular, cubic, or pyramidal. In chemiluminescence and fluorescence-based assays, the tip 301 can serve as a convenient means to present the assay product to the assay optics.
  • Figure 3B demonstrates an exemplary sample collection unit 302 comprising a sample tip 302 .
  • the sample tip 302 as shown in Figure 3B can also be separate from a sample collection unit 302 and used to transfer sample from the sample collection units to other units on a device as described herein.
  • the sample tip as shown in Figure 3B comprises a boss 322 as described herein to couple the tip 302 with a housing of a device and a fluid transfer device.
  • the sample tip 302 also comprises an opening 332 to allow the transfer of fluids or samples in and out of the sample tip.
  • the sample tip 302 is of the same shape as an assay tip 301 . In other embodiments (such as those shown in Figures 3A and 3B ), the sample tip 302 is a different shape than the assay tip 301 .
  • one function of a tip is to enable samples and liquid reagents to be brought into contact with the capture surface of the assay unit.
  • the movement can occur by a variety of means including, but not limited to, capillary action, aspiration, and controlled pumping.
  • the small size of the tips enables rapid control of the required temperature for a chemical reaction. Heat transfer and/or maintenance can be carried out by simply placing the tip in a temperature controlled block.
  • the tip is able to contain about 1 to 40 microliters of fluid. In a further embodiment, the tip is able to contain about 5 to 25 microliters of fluid. In an embodiment, the tip contains 20 microliters of fluid. In some instances, a tip can contain 1 microliter of fluid or less. In other instances, a tip can contain up to 100 microliters.
  • the end of the tip can be blotted onto an absorbent material (for example incorporated into a disposable cartridge) prior to introduction of the next assay component to avoid contamination with a small amount of sample and/or reagent. Due to physical forces, any liquid drawn into a subject tip can be held at any desired location with minimal risk of the liquid draining out, even when held in a vertical orientation.
  • an absorbent material for example incorporated into a disposable cartridge
  • the assay unit for example, an assay tip
  • assay capture reagents prior to use, using similar fluidics as in the assay (for example, controlled capillary or mechanical aspiration).
  • a capture surface (also referred to herein as a reaction site) can be formed by a binding antibody or other capture reagents bound covalently or by adsorption to the assay unit. The surface can then dried and maintained in dry condition until used in an assay. In an embodiment, there is a reaction site for each analyte to be measured.
  • the assay unit can be moved into fluid communication with the reagent unit and/or a sample collection unit, such that a reagent or sample can interact with a reaction site where bound probes can detect an analyte of interest in the bodily fluid sample.
  • a reaction site can then provide a signal indicative of the presence or concentration of the analyte of interest, which can then be detected by a detection device described herein.
  • the location and configuration of a reaction site is an important element in an assay device.
  • disposable immunoassay devices have been configured with their capture surface as an integral part of the device.
  • a molded plastic assay unit is either commercially available or can be made by injection molding with precise shapes and sizes.
  • the characteristic dimension can be a diameter of 0.05 - 3 mm or can be a length of 3 to 30 mm.
  • the units can be coated with capture reagents using method similar to those used to coat microtiter plates but with the advantage that they can be processed in bulk by placing them in a large vessel, adding coating reagents and processing using sieves, holders, and the like to recover the pieces and wash them as needed.
  • the assay unit can offer a rigid support on which a reactant can be immobilized.
  • the assay unit is also chosen to provide appropriate characteristics with respect to interactions with light.
  • the assay unit can be made of a material, such as functionalized glass, Si, Ge, GaAs, GaP, SiO 2 , SiN 4 , modified silicon, or any one of a wide variety of gels or polymers such as (poly)tetrafluoroethylene, (poly)vinylidenedifluoride, polystyrene, polycarbonate, polypropylene, PMMA, ABS, or combinations thereof.
  • an assay unit comprises polystyrene.
  • Other appropriate materials may be used in accordance with the present invention.
  • a transparent reaction site may be advantageous.
  • the surface may be advantageously opaque and/or preferentially light scattering.
  • a reactant immobilized at the capture surface can be anything useful for detecting an analyte of interest in a sample of bodily fluid.
  • reactants include, without limitation, nucleic acid probes, antibodies, cell membrane receptors, monoclonal antibodies and antisera reactive with a specific analyte.
  • Various commercially available reactants such as a host of polyclonal and monoclonal antibodies specifically developed for specific analytes can be used.
  • the immobilization may be covalent or noncovalent, via a linker moiety, or tethering them to an immobilized moiety.
  • Non-limiting exemplary binding moieties for attaching either nucleic acids or proteinaceous molecules such as antibodies to a solid support include streptavidin or avidin/biotin linkages, carbamate linkages, ester linkages, amide, thiolester, (N)-functionalized thiourea, functionalized maleimide, amino, disulfide, amide, hydrazone linkages, and among others.
  • a silyl moiety can be attached to a nucleic acid directly to a substrate such as glass using methods known in the art.
  • Surface immobilization can also be achieved via a Poly-L Lysine tether, which provides a charge-charge coupling to the surface.
  • the assay units can be dried following the last step of incorporating a capture surface.
  • drying can be performed by passive exposure to a dry atmosphere or via the use of a vacuum manifold and/or application of clean dry air through a manifold.
  • an assay unit is designed to enable the unit to be manufactured in a high volume, rapid manufacturing processes.
  • tips can be mounted in large-scale arrays for batch coating of the capture surface into or onto the tip.
  • tips can be placed into a moving belt or rotating table for serial processing.
  • a large array of tips can be connected to vacuum and/or pressure manifolds for simple processing.
  • an assay unit can be operably coupled with a fluid transfer device.
  • the fluid transfer device can be operated under automatic control without human interaction.
  • the control of the installed height of a disposable liquid tip relies on the tapered interference attachment of the tip to the liquid dispenser.
  • a fluid transfer device can engage the tip.
  • the immersion length of a tip in liquid to be transferred must be known to minimize the liquid contact with the outside of the tip which may be uncontrolled.
  • a hard stop can be molded at the bottom of the tapered connector which engages the nozzle of the dispenser.
  • An air tight seal can be made by an o-ring that is half way up the taper or in the flat bottom of the nozzle. By separating the seal function of the tip from the controlled height of the tip both can be separately adjusted.
  • the modular device and fluid transfer device can enable many assays to be performed in parallel.
  • the reagent units of a device can store reagents that are required to perform a give chemical reaction for detecting a given analyte of interest.
  • Liquid reagents can be dispensed into small capsules that can be manufactured from a variety of materials including, without limitation, plastic such as polystyrene, polyethylene, or polypropylene.
  • the reagent units are cylindrical cups. Two examples of a reagent unit 401, 402 comprising a cup are shown in Figures 4A and 4B . Where desired, the units 401, 402 fit snugly into cavities in a housing of a device. The units 401, 402 can be sealed on the open surface to avoid spilling the reagents 411, 412 onboard.
  • the seal is an aluminized plastic and can be sealed to the cup by thermal bonding.
  • a unit can be of any shape as is necessary to contain a reagent.
  • a cylindrical shaped reagent unit 401 is shown in Figure 4A , and the reagent unit contains a liquid reagent 411.
  • a different shaped reagent unit 402 is illustrated in Figure 4B also contain a liquid reagent 412 .
  • Both exemplary reagent units 401, 402 comprise optional slight modifications near the top surface that allow the units 401, 402 to fit snugly into a housing of a device as described herein.
  • the reagent units are modular.
  • the reagent unit can be designed to enable the unit to be manufactured in a high volume, rapid manufacturing processes. For example, many reagent units can be filled and sealed in a large-scale process simultaneously.
  • the reagent units can be filled according to the type of assay or assays to be run by the device. For example, if one user desires different assays than another user, the reagent units can be manufactured accordingly to the preference of each user, without the need to manufacture an entire device.
  • reagent units can be placed into a moving belt or rotating table for serial processing.
  • the reagent units are accommodated directly into cavities in the housing of a device.
  • a seal can be made onto areas of housing surrounding the units.
  • Reagents according to the present invention include without limitation wash buffers, enzyme substrates, dilution buffers, conjugates, enzyme-labeled conjugates, DNA amplifiers, sample diluents, wash solutions, sample pre-treatment reagents including additives such as detergents, polymers, chelating agents, albumin-binding reagents, enzyme inhibitors, enzymes, anticoagulants, red-cell agglutinating agents, antibodies, or other materials necessary to run an assay on a device.
  • An enzyme-labeled conjugate can be either a polyclonal antibody or monoclonal antibody labeled with an enzyme that can yield a detectable signal upon reaction with an appropriate substrate.
  • the reagents comprise immunoassay reagents.
  • reagents especially those that are relatively unstable when mixed with liquid, are confined separately in a defined region (for example, a reagent unit) within the device.
  • a reagent unit contains approximately about 5 microliters to about 1 milliliter of liquid. In some embodiments, the unit may contain about 20-200 microliters of liquid. In a further embodiment, the reagent unit contains 100 microliters of fluid. In an embodiment, a reagent unit contains about 40 microliters of fluid.
  • the volume of liquid in a reagent unit may vary depending on the type of assay being run or the sample of bodily fluid provided. In an embodiment, the volumes of the reagents do not have to predetermined, but must be more than a known minimum. In some embodiments, the reagents are initially stored dry and dissolved upon initiation of the assay being run on the device.
  • the reagent units can be filled using a siphon, a funnel, a pipette, a syringe, a needle, or a combination thereof.
  • the reagent units may be filled with liquid using a fill channel and a vacuum draw channel.
  • the reagent units can be filled individually or as part of a bulk manufacturing process.
  • an individual reagent unit comprises a different reagent as a means of isolating reagents from each other.
  • the reagent units may also be used to contain a wash solution or a substrate.
  • the reagent units may be used to contain a luminogenic substrate.
  • a plurality of reagents are contained within a reagent unit.
  • the setup of the device enables the capability of pre-calibration of assay units and the reagent units prior to assembly of disposables of the subject device.
  • a system of the invention comprises a device comprising assay units and reagent units comprising reagents (both liquid and solid phase reagents).
  • reagents both liquid and solid phase reagents
  • at least one of the whole device, an assay unit, a reagent unit, or a combination thereof is disposable.
  • the detection of an analyte with a device is operated by an instrument.
  • the instrument, device, and method offer an automated detection system.
  • the automated detection system can be automated based upon a defined protocol or a protocol provided to the system by a user.
  • a system for automated detection an analyte in a bodily fluid sample comprises a device or cartridge, and a detection assembly or detector for detecting the detectable signal indicative of the presence or absence of the analyte.
  • the user applies a sample (for example, a measured or an unmeasured blood sample) to the device and inserts the device into the instrument. All subsequent steps are automatic, programmed either by the instrument (hard wired), the user, a remote user or system, or modification of the instrument operation according to a identifier (for example, a bar code or RFID on the device).
  • a sample for example, a measured or an unmeasured blood sample
  • Examples of different functions of that can be carried out using a system of the invention include, but are not limited to, dilution of a sample, removal of parts of a sample (for example, red blood cells (RBCs)), reacting a sample in an assay unit, adding liquid reagents to the sample and assay unit, washing the reagents from the sample and assay unit, and containing liquids during and following use of the device.
  • Reagents can be onboard the device in a reagent unit or in a reagent unit to assembled onto the device.
  • An automated system can detect a particular analyte in a biological sample (for example, blood) by an enzyme-linked immunosorbent assay (ELISA).
  • ELISA enzyme-linked immunosorbent assay
  • the system is amenable to multiplexing and is particularly suited for detecting an analyte of interest present in a small volume of a whole blood sample (for example, 20 microliters or less).
  • the system can also detect analytes in different dilutions of a single sample, allowing different sensitivities to be tested on the same device, when desired. All reagents, supplies, and wastes can be contained on the device of the system.
  • a sample from a subject is applied to the assembled device and the device is inserted into an instrument.
  • an instrument can begin processing the sample by some combination of removal of red cells (blood sample), dilution of the sample, and movement the sample to the assay unit.
  • a plurality of assay units are used and a portion of the sample is moved to individual assay units in sequence or in parallel. Assays can then be performed by a controlled sequence of incubations and applications of reagents to the capture surfaces.
  • An exemplary fluid transfer device is comprised of any component required to perform and/or read the assay.
  • Example of components include, but are not limited to, pumps to aspirate and eject accurately known fluid volumes from wells or units of the device, at least one translational stage for improving the precision and accuracy of the movement within the system, a detector to detect an analyte in an assay unit, and temperature regulation means to provide a regulated temperature environment for incubation of assays.
  • the instrument controls the temperature of the device.
  • the temperature is in the range of about 30-40 degrees Celsius.
  • the temperature control by the system can comprise active cooling.
  • the range of temperature is about 0-100 degrees Celsius.
  • temperatures up to 100 degrees Celsius can be achieved.
  • the temperature range is about 15-50 degrees Celsius.
  • a temperature control unit of the system can comprise a thermoelectric device, such as a Peltier device.
  • Cartridges, devices, and systems as described herein can offer many features that are not available in existing POC systems or integrated analysis systems. For example, many POC cartridges rely on a closed fluidic system or loop to handle small volumes of liquid in an efficient manner.
  • the cartridges and fluidic devices described herein can have open fluid movement between units of the cartridge.
  • a reagent can be stored in a unit, a sample in a sample collection unit, a diluent in a diluent unit, and the capture surface can be in an assay unit, wherein in one state of cartridge, none of the units are in fluid communication with any of the other units.
  • the units do not have to be in fluid communication with each other in a state.
  • the units can be movable relative to each other in order to bring some units into fluid communication.
  • a fluid transfer device can comprise a head that engages an assay unit and moves the assay unit into fluidic communication with a reagent unit.
  • the devices and systems herein can provide an effective means for high throughput and real-time detection of analytes present in a bodily fluid from a subject.
  • the detection methods may be used in a wide variety of circumstances including identification and quantification of analytes that are associated with specific biological processes, physiological conditions, disorders or stages of disorders.
  • the systems have a broad spectrum of utility in, for example, drug screening, disease diagnosis, phylogenetic classification, parental and forensic identification, disease onset and recurrence, individual response to treatment versus population bases, and monitoring of therapy.
  • the subject devices and systems are also particularly useful for advancing preclinical and clinical stage of development of therapeutics, improving patient compliance, monitoring ADRs associated with a prescribed drug, developing individualized medicine, outsourcing blood testing from the central laboratory to the home or on a prescription basis, and monitoring therapeutic agents following regulatory approval.
  • the devices and systems can provide a flexible system for personalized medicine. Using the same system, a device can be changed or interchanged along with a protocol or instructions to a programmable processor of the systems to perform a wide variety of assays as described.
  • the systems and devices herein offer many features of a laboratory setting in a desk-top or smaller size automated instrument.
  • a patient may be provided with a plurality of devices to be used for detecting a variety of analytes.
  • a subject may, for example, use different fluidic devices on different days of the week
  • the software on the external device associating the identifier with a protocol may include a process to compare the current day with the day the fluidic device is to be used based on a clinical trial for example.
  • the patient is provided different reagent units and assay units that can be fit into a housing of a device interchangeably.
  • the system can be programmed or reprogrammed by downloading new instructions from, e.g. an external device such as a server.
  • the external device can wirelessly send notification to the subject using any of the methods described herein or known in the art to notify them of the proper device and/or proper instructions for the system.
  • This example is only illustrative and can easily be extended to, for example, notifying a subject that a fluidic device is not being used at the correct time of day.
  • a cartridge as illustrated in Figure 1 can comprise a variety of assay units and reagent units.
  • the assay units can comprise a capture surface according to an analyte to be detected.
  • the assay units can then be assembled with the rest of the device in a just-in-time fashion.
  • the capture surface is integral to the device and if the capture surface is incorrect or not properly formed, the whole device is bad.
  • the capture surface and/or assay unit can be individually quality controlled and customized independently of the reagent units and the housing of the device.
  • Reagent units can be filled with a variety of reagents in a similar just-in-time fashion. This provides flexibility of the device being customizable. In addition, the reagent units can be filled with different volumes of reagents without affecting the stability of a device or the chemical reactions to be run within the device. Coupled with a system as described with a fluid transfer device, the devices and units described herein offer flexibility in the methods and protocols of the assays to be run. For example, a batch of similar devices containing the same reagents can be given to a patient pool for a clinical trial. Half way through the clinical trial, a user identifies that the assay could be optimized by changing the dilution of the sample and the amount of reagent provided to the assay unit.
  • the assay can be changed or optimized by only changing the instructions to a programmable processor of the fluid transfer device.
  • the batch of cartridges in the patient pool had excess diluent loaded on the cartridge.
  • the new protocol demands four times as much diluent as the previous protocol. Due to the methods and systems provided herein, the protocol can be changed at a central server and sent to all the systems for executing the methods with the devices without having to provide new devices to the patient pool.
  • a POC device and system as described herein can offer much of the flexibility of a standard laboratory practice where excess reagents and often excess sample are often available.
  • a cartridge can be configured to run 8 assays using an array of assay units and an array of reagent units. Due to the features of the cartridge as described herein, the same housing, or a housing of the same design can be used to manufacture a cartridge with up to 8 different assays than the previous cartridge. This flexibility is difficult to achieve in many current POC device designs because of the closed systems and fluid channels, and therefore the devices may not be modular or as easy to assemble as described.
  • the system as described herein has the ability to simultaneously assay analytes that are present in the same sample in a wide concentration range.
  • Another advantage for being able to detect concentrations of different analytes present in a wide concentration range is the ability to relate the ratios of the concentration of these analytes to safety and efficacy of multiple drugs administered to a patient. For example, unexpected drug-drug interactions can be a common cause of adverse drug reactions. A real-time, concurrent measurement technique for measuring different analytes would help avoid the potentially disastrous consequence of adverse drug-drug interactions.
  • the data generated with the use of the subject fluidic devices and systems can be utilized for performing a trend analysis on the concentration of an analyte in a subject.
  • a system as provided herein is configured to run multiple (e.g., five or more) different target analyte detection assays.
  • a sample In order to bring the expected analyte concentration within the range of detection of an immunoassay as described herein and commonly used in the POC field, a sample must be diluted e.g., 3:1, 8:1, 10:1, 100:1, and 2200:1, to run each of the five assays. Because the fluid transfer device is able to hold and move fluid within the device, serial dilutions can be performed with a system as described herein to achieve these five different dilutions and detect all five different target analytes. As described above, the protocol for performing the assays is also capable of being adjusted without modifying the device or the system.
  • a laboratory setting with traditional pipetting typically larger volumes of sample are used than in a POC setting.
  • a laboratory may analyze a blood sample withdrawn from the arm of a patient in a volume in the milliliter range.
  • many devices and users demand that the process is fast, easy and/or minimally invasive, therefore, small samples (on the order of a volume in the microliter range) such as one obtained by a fingerstick) are typically analyzed by a POC device.
  • small samples on the order of a volume in the microliter range
  • current POC devices can lose flexibility in running an assay that is afforded in a laboratory setting. For example, to run multiple assays from a sample, a certain minimum volume can be required for each assay to allow for accurate detection of an analyte, therefore putting some limits on a device in a POC setting.
  • a system and/or fluid transfer device as described herein provides a great deal of flexibility.
  • the fluid transfer device can be automated to move an assay unit, an assay tip, or an empty pipette from one unit of the device to a separate unit of the device, not in fluid communication with each other. In some instances, this can avoid cross-contamination of the units of a device as described. In other instances, it allows for the flexibility of moving several fluids within a device as described into contact with each other according to a protocol or instructions. For example, a cartridge comprising 8 different reagents in 8 different reagent units can be addressed and engaged by a fluid transfer device in any order combination as is instructed by a protocol.
  • the assay protocol can be different or modified without the need for a second cartridge or a second system.
  • a user orders a cartridge with a specific type of capture surface and specific reagents to run an assay to detect an analyte (for example, C-reactive protein (CRP)) in a sample.
  • the protocol the user originally planned for may require 2 washing steps and 3 dilution steps. After the user has received the device and system, the user has decided that the protocol should actually have 5 washing steps and only 1 dilution step.
  • the devices and systems herein can allow the flexibility for this change in protocol without having to reconfigure the device or the system. In this example, only a new protocol or set of instructions are needed to be sent to the programmable processor of the system or the fluid transfer device.
  • a system as provided herein is configured to run five different target analyte detection assays, wherein each assay needs to be incubated at a different temperature.
  • incubation of multiple assays at different temperatures is a difficult task because the multiple assays are not modular and the capture surfaces cannot be moved relative to the heating device.
  • an individual assay unit can be place in an individual heating unit.
  • a system comprises a plurality of heating units.
  • a system comprises at least as many heating units as assay units. Therefore, a plurality of assays can be run as a plurality of temperatures.
  • Systems and devices as described herein can also provide a variety of quality control measures not previously available with many prior art POC devices.
  • the assay units and reagents units can be quality controlled separately from each other and/or separately from the housing and/or separately from a system or fluid transfer device. Exemplary methods and systems of quality control offered by the systems and devices herein are described.
  • a system as described can run a variety of assays, regardless of the analyte being detected from a bodily fluid sample.
  • a protocol dependent on the identity of the device may be transferred from an external device where it can be stored to a reader assembly to enable the reader assembly to carry out the specific protocol on the device.
  • the device has an identifier (ID) that is detected or read by an identifier detector described herein.
  • the identifier detector can communicate with a communication assembly via a controller which transmits the identifier to an external device. Where desired, the external device sends a protocol stored on the external device to the communication assembly based on the identifier.
  • the protocol to be run on the system may comprise instructions to the controller of the system to perform the protocol, including but not limited to a particular assay to be run and a detection method to be performed.
  • a signal indicative of an analyte in the bodily fluid sample is generated and detected by a detection assembly of the system.
  • the detected signal may then be communicated to the communications assembly, where it can be transmitted to the external device for processing, including without limitation, calculation of the analyte concentration in the sample.
  • the identifier may be a bar code identifier with a series of black and white lines, which can be read by an identifier detector such as a bar code reader, which are well known. Other identifiers could be a series of alphanumerical values, colors, raised bumps, or any other identifier which can be located on a device and be detected or read by an identifier detector.
  • the identifier detector may also be an LED that emits light which can interact with an identifier which reflects light and is measured by the identifier detector to determine the identity of a device.
  • the identifier may comprise a storage or memory device and can transmit information to an identification detector. In some embodiments a combination of techniques may be used. In some embodiments, the detector is calibrated by used of an optical source, such as an LED.
  • a bodily fluid sample can be provided to a device, and the device can be inserted into a system.
  • the device is partially inserted manually, and then a mechanical switch in the reader assembly automatically properly positions the device inside the system. Any other mechanism known in the art for inserting a disk or cartridge into a system may be used. In some embodiments, manual insertion may be required.
  • a method of automatically selecting a protocol to be run on a system comprises providing a device comprising an identifier detector and an identifier; detecting the identifier; transferring said identifier to an external device; and selecting a protocol to be run on the system from a plurality of protocols on said external device associated with said identifier.
  • a system for automated detection of a plurality of analytes in a bodily fluid sample comprises: a fluidic device (such as those described herein) comprising: a sample collection unit configured to contain the bodily fluid sample; an array of assay units, wherein an individual assay unit of said array of assay units is configured to run a chemical reaction that yields a signal indicative of an individual analyte of said plurality of analytes being detected; and an array of reagent units, wherein an individual reagent unit of said array of reagent units contains a reagent.
  • the system further comprises a fluid transfer device comprising a plurality of heads, wherein an individual head of the plurality of heads is configured to engage the individual assay unit, and wherein said fluid transfer device comprises a programmable processor configured to direct fluid transfer of the bodily fluid sample from the sample collection unit and the reagent from the individual reagent unit into the individual assay unit.
  • a fluid transfer device comprising a plurality of heads, wherein an individual head of the plurality of heads is configured to engage the individual assay unit, and wherein said fluid transfer device comprises a programmable processor configured to direct fluid transfer of the bodily fluid sample from the sample collection unit and the reagent from the individual reagent unit into the individual assay unit.
  • an individual assay unit comprises a reagent and is configured is to run a chemical reaction with that reagent.
  • the configuration of the processor to direct fluid transfer effects a degree of dilution of the bodily fluid sample in the array of assay units to bring signals indicative of the plurality of analytes being detected within a detectable range, such that said plurality of analytes are detectable with said system.
  • the bodily fluid sample comprises at least two analytes that are present at concentrations that differ by at least 2, 5, 10, 15, 50, or 100 orders of magnitude.
  • the bodily fluid sample is a single drop of blood.
  • the concentrations of at least two analytes present in a sample differs by up to 10 orders of magnitude (for example, a first analyte is present at 0.1 pg/mL and a second analyte is present at 500 ug/mL.
  • some protein analytes are found at concentrations of greater than 100 mg/mL, which can extend the range of interest to about twelve orders of magnitude.
  • a degree of dilution of the bodily fluid sample can bring the signals indicative of the at least two analytes within the detectable range.
  • a system further comprises a detector, such as a photomultiplier (PMT).
  • PMT photomultiplier
  • a detectable range of the detector can be about 10 to about 10 million counts per second. Each count corresponds to a single photon.
  • PMTs are not 100% efficient and the observed count rate may be slightly lower than, but still close to, the actual number of photons reaching the detector per unit time.
  • counts are measured in about ten intervals of about one second and the results are averaged.
  • ranges for assays are 1000 - 1,000,000 counts per second when using a PMT as a detector. In some instances, count rates as low as 100 per second and count rates as high as 10,000,000 are measurable.
  • the linear response range of PMTs (for example, the range where count rate is directly proportional to number of photons per unit time) can be about 1000-3,000,000 counts per second.
  • an assay has a detectable signal on the low end of about 200-1000 counts per second and on the high end of about 10,000-2,000,000 counts per second.
  • the count rate is directly proportional to alkaline phosphatase bound to the capture surface and also directly proportional to the analyte concentration.
  • exemplary detectors include avalanche photodiodes, avalanche photodiode arrays, CCD arrays, super-cooled CCD arrays. Many other detectors have an output that is digital and generally proportional to photons reaching the detector. The detectable range for exemplary detectors can be suitable to the detector being used.
  • An individual head of a fluid transfer device can be configured to adhere to the individual assay unit.
  • the fluid transfer device can be a pipette, such as an air-displacement pipette.
  • the fluid transfer device can be automated.
  • a fluid transfer device can further comprise a motor in communication with a programmable processor and the motor can move the plurality of heads based on a protocol from the programmable processor.
  • an individual assay unit can be a pipette tip, for example, a pipette tip with a capture surface or reaction site.
  • the dilution factor must be estimated and reasonably precise. For example, in environments where non-expert users operate the system there needs to be ways of ensuring a dilution of a sample.
  • a fluid transfer device can affect a degree of dilution of a sample to provide accurate assay results.
  • a programmable fluid transfer device can be multi-headed) to dilute or serially dilute samples as well as provide mixing of a sample and diluent.
  • a fluid transfer device can also provide fluid movement in POC devices.
  • the systems and devices herein can enable many features of the flexibility of laboratory setting in a POC environment. For example, samples can be collected and manipulated automatically in a table top size or smaller device or system.
  • a common issue in POC devices is achieving different dilution ranges when conducting a plurality of assays, wherein the assays may have significantly different sensitivity or specificity. For example, there may be two analytes in a sample, but one analyte has a high concentration in the sample and the other analyte has a very low concentration.
  • the systems and devices herein can dilute the sample to significantly different levels in order to detect both analytes.
  • a sample can be serially diluted to the appropriate detection range and provided to a capture surface for detection.
  • a sample with an analyte in a low concentration may not need to be diluted.
  • the assay range of the POC devices and systems provided herein can be expanded from many of the current POC devices.
  • a fluid transfer device can be part of a system that is a bench-top instrument.
  • the fluid transfer device can comprise a plurality of heads. Any number of heads as is necessary to detect a plurality of analytes in a sample is envisioned for a fluid transfer device of the invention.
  • a fluid transfer device has about eight heads mounted in a line and separated by a distance.
  • the heads have a tapered nozzle that engages by press fitting with a variety of tips, such as assay unit or sample collection units as described herein.
  • the tips can have a feature that enables them to be removed automatically by the instrument and disposed into in a housing of a device as described after use.
  • the assay tips are clear and transparent and can be similar to a cuvette within which an assay is run that can be detected by an optical detector such as a photomultiplier tube.
  • the programmable processor of a system can comprise instructions or commands and can operate a fluid transfer device according to the instructions to transfer liquid samples by either withdrawing (for drawing liquid in) or extending (for expelling liquid) a piston into a closed air space. Both the volume of air moved and the speed of movement can be precisely controlled, for example, by the programmable processor.
  • Mixing of samples (or reagents) with diluents (or other reagents) can be achieved by aspirating components to be mixed into a common tube and then repeatedly aspirating a significant fraction of the combined liquid volume up and down into a tip. Dissolution of reagents dried into a tube can be done is similar fashion.
  • Incubation of liquid samples and reagents with a capture surface on which is bound a capture reagent (for example an antibody) can be achieved by drawing the appropriate liquid into the tip and holding it there for a predetermined time. Removal of samples and reagents can be achieved by expelling the liquid into a reservoir or an absorbent pad in a device as described. Another reagent can then be drawn into the tip according to instructions or protocol from the programmable processor.
  • a liquid 1111 previously in a tip 1101 can leave a thin film 1113 within the tip 1101 when expelled. Therefore, a system can use the action of the leading (for example uppermost) portion of the next liquid 1112 to scour the previously present liquid 1111 from the tip 1101 . The portion of the subsequent liquid contaminated with the liquid previously present 1113 can be held within the top of the tip 1101 where it does not continue to interact with the capture surface 1102 .
  • the capture surface 1102 can be in a defined area of the tip 1101 such that the previous liquid 1111 does not react with the capture surface 1102 , for example as shown in Figure 11 , the capture surface 1102 occupies a defined portion of the cylindrical part of the tip 1101 not extending all the way up to the boss of the tip.
  • incubation time is short (for example 10 minutes) and separation of the contaminated zone of liquid is relatively large (> 1 mm) so diffusion or the active components of the contaminated portion of liquid 1113 does not occur rapidly enough react with the capture surface 1102 during the incubation.
  • there is a requirement to remove one reagent or wash the capture surface for example, a detector antibody which is labeled with the assay signal generator).
  • a fluid transfer device of a system described herein can provide washing by adding further removal and aspiration cycles of fluid transfer, for example, using a wash reagent.
  • four wash steps demonstrated that the unbound detector antibody in contact with the capture surface is reduced by a factor of better than 10 6 -fold. Any detector antibody non-specifically bound to the capture surface (highly undesirable) can also be removed during this wash process.
  • Extension of the range of an assay can be accomplished by dilution of the sample.
  • POC assay systems using disposable cartridges containing the diluent there is often a practical limit to the extent of dilution. For example, if a small blood sample is obtained by fingerstick (for example, about 20 microliters) is to be diluted and the maximum volume of diluent that can be placed in a tube is 250 microliters, the practical limit of dilution of the whole sample is about 10-fold. In an example herein, a system can aspirate a smaller volume of the sample (for example about 2 microliters) making the maximum dilution factor about 100-fold.
  • Separation-based ELISA assays can have an intrinsic limitation in thee capacity of the capture surface to bind the analyte (for example about a few hundred ng/ml for a typical protein analyte). Some analytes are present in blood at hundreds of micrograms/ml. Even when diluted by 100-fold, the analyte concentration may be outside the range of calibration.
  • multiple dilutions can be achieved by performing multiple fluid transfers of the diluent into an individual assay unit or sample collection unit. For example, if the concentration of an analyte is very high in a sample as described above, the sample can be diluted multiple times until the concentration of the analyte is within an acceptable detection range.
  • the systems and methods herein can provide accurate measurements or estimations of the dilutions in order to calculate the original concentration of the analyte.
  • a system herein can move a liquid sample and move an assay unit.
  • a system can comprise a heating block and a detector.
  • a system may provide aspiration-, syringe-, or pipette-type action.
  • a fluid transfer device for moving a liquid sample is a pipette and pipette head system.
  • the number of pipette devices required by the system can be adjusted according to the type of analyte to be detected and the number of assays being run.
  • the actions performed by the pipette system can be automated or operated manually by a user.
  • Figure 5 demonstrates an example of a fluid transfer device 520 and system 500 as described herein.
  • the fluid transfer device system can move eight different or identical volumes of liquid simultaneously using the eight different heads 522 .
  • the cartridge (or device as described herein) 510 comprises eight assay units 501 .
  • Individual assay units 501 are configured according to the type of assay to be run within the unit 501 .
  • Individual assay units 501 may require a certain volume of sample.
  • An individual head 522 can be used to distribute a proper amount of sample to an individual assay unit 501 .
  • each head 522 corresponds to an addressed individual assay unit 501 .
  • the fluid transfer device mechanism 520 can also be used to distribute reagents from the reagent units.
  • Different types of reagents include a conjugate solution, a wash solution, and a substrate solution.
  • the stage 530 on which the device 510 sits can be moved to move the device 510 relative to the positioning of the assay units 501 and heads 522 and according to the steps necessary to complete an assay as demonstrated in Figure 5 .
  • the heads 522 and tips 501 or the fluid transfer device 520 can be moved relative to the position of the device 510 .
  • a reagent is provided in dry form and rehydrated and/or dissolved during the assy. Dry forms include lyophilized materials and films coated on surfaces.
  • a system can comprise a holder or engager for moving the assay units or tips.
  • An engager may comprise a vacuum assembly or an assembly designed to fit snugly into a boss of an assay unit tip.
  • a means for moving the tips can be moved in a manner similar to the fluid transfer device heads. The device can also be moved on a stage according to the position of an engager or holder.
  • an instrument for moving the tips is the same as an instrument for moving a volume of sample, such as a fluid transfer device as described herein.
  • a sample collection tip can be fit onto a pipette head according to the boss on the collection tip.
  • the collection tip can then be used to distribute the liquid throughout the device and system.
  • the collection dip can be disposed, and the pipette head can be fit onto an assay unit according to the boss on the assay unit.
  • the assay unit tip can then be moved from reagent unit to reagent unit, and reagents can be distributed to the assay unit according to the aspiration-or pipette-type action provided by the pipette head.
  • the pipette head can also perform mixing within a collection tip, assay unit, or reagent unit by aspiration- or syringe-type action.
  • a system can comprise a heating block for heating the assay or assay unit and/or for control of the assay temperature. Heat can be used in the incubation step of a assay reaction to promote the reaction and shorten the duration necessary for the incubation step.
  • a system can comprise a heating block configured to receive an assay unit of the invention.
  • the heating block can be configured to receive a plurality of assay units from a device of the invention. For example, if 8 assays are desired to be run on a device, the heating block can be configured to receive 8 assay units.
  • assay units can be moved into thermal contact with a heating block using the means for moving the assay units. The heating can be performed by a heating means known in the art.
  • the system 600 comprises a translational stage 630 onto which a device 610 (or cartridge in this example) is placed either manually or automatically or a combination of both.
  • the system 600 also comprises a heating block 640 that can be aligned with the assay units 611 of the device 610 .
  • the device 610 comprises a series of 8 assay units 611 and multiple corresponding reagent units 612
  • the heating block 640 also comprises an area 641 for at least 8 units to be heated simultaneously.
  • Each of the heating areas 641 can provide the same or different temperatures to each individual assay unit 611 according to the type of assay being run or the type of analyte being detected.
  • the system 600 also comprises a detector (such as a photomultiplier tube) 650 for detection of a signal from an assay unit 611 representative of the detection of an analyte in a sample.
  • a sensor is provided to locate an assay unit relative to a detector when an assay is detected.
  • the detector is a reader assembly housing a detection assembly for detecting a signal produced by at least one assay on the device.
  • the detection assembly may be above the device or at a different orientation in relation to the device based on, for example, the type of assay being performed and the detection mechanism being employed.
  • the detection assembly can be moved into communication with the assay unit or the assay unit can be moved into communication with the detection assembly.
  • an optical detector is provided and used as the detection device.
  • Non-limiting examples include a photodiode, photomultiplier tube (PMT), photon counting detector, avalanche photo diode, or charge-coupled device (CCD).
  • a pin diode may be used.
  • a pin diode can be coupled to an amplifier to create a detection device with a sensitivity comparable to a PMT.
  • Some assays may generate luminescence as described herein.
  • chemiluminescence is detected.
  • a detection assembly could include a plurality of fiber optic cables connected as a bundle to a CCD detector or to a PMT array.
  • the fiber optic bundle could be constructed of discrete fibers or of many small fibers fused together to form a solid bundle. Such solid bundles are commercially available and easily interfaced to CCD detectors.
  • a detector can also comprise a light source, such as a bulb or light emitting diode (LED).
  • the light source can illuminate an assay in order to detect the results.
  • the assay can be a fluorescence assay or an absorbance assay, as are commonly used with nucleic acid assays.
  • the detector can also comprise optics to deliver the light source to the assay, such as a lens or fiber optics.
  • the detection system may comprise non-optical detectors or sensors for detecting a particular parameter of a subject.
  • sensors may include temperature, conductivity, potentiometric signals, and amperometric signals, for compounds that are oxidized or reduced, for example, O 2 , H 2 O 2 , and I 2 , or oxidizable/reducible organic compounds.
  • a device and system may, after manufacturing, be shipped to the end user, together or individually.
  • the device or system of the invention can be packaged with a user manual or instructions for use.
  • the system of the invention is generic to the type of assays run on different devices. Because components of the device can be modular, a user may only need one system and a variety of devices or assay units or reagent units to run a multitude of assays in a point-of-care environment. In this context, a system can be repeatedly used with multiple devices, and it may be necessary to have sensors on both the device and the system to detect such changes during shipping, for example.
  • a sensor located on either the device or system can relay these changes to, for example, the external device so that adjustments can be made during calibration or during data processing on the external device. For example, if the temperature of a fluidic device is changed to a certain level during shipping, a sensor located on the device could detect this change and convey this information to the system when the device is inserted into the system by the user. There may be an additional detection device in the system to perform these tasks, or such a device may be incorporated into another system component. In some embodiments information may be wirelessly transmitted to either the system or the external device, such as a personal computer or a television. Likewise, a sensor in the system can detect similar changes.
  • a sensor in the shipping packaging as well, either instead of in the system components or in addition thereto.
  • adverse conditions that would render an assay cartridge or system invalid that can be sensed can include exposure to a temperature higher than the maximum tolerable or breach of the cartridge integrity such that moisture penetration.
  • the system comprises a communication assembly capable of transmitting and receiving information wirelessly from an external device.
  • wireless communication may be Bluetooth or RTM technology.
  • Various communication methods can be utilized, such as a dial-up wired connection with a modem, a direct link such as a T1, ISDN, or cable line.
  • a wireless connection is established using exemplary wireless networks such as cellular, satellite, or pager networks, GPRS, or a local data transport system such as Ethernet or token ring over a local area network.
  • the information is encrypted before it is transmitted over a wireless network.
  • the communication assembly may contain a wireless infrared communication component for sending and receiving information.
  • the system may include integrated graphic cards to facilitate display of information.
  • the communication assembly can have a memory or storage device, for example localized RAM, in which the information collected can be stored.
  • a storage device may be required if information can not be transmitted at a given time due to, for example, a temporary inability to wirelessly connect to a network.
  • the information can be associated with the device identifier in the storage device.
  • the communication assembly can retry sending the stored information after a certain amount of time.
  • an external device communicates with the communication assembly within the reader assembly.
  • An external device can wirelessly or physically communicate with a system, but can also communicate with a third party, including without limitation a patient, medical personnel, clinicians, laboratory personnel, or others in the health care industry.
  • a patient delivers a blood sample to a device as described herein and then the device is inserted into a reader, wherein the reader can be desktop system capable of reading an analyte in the blood sample.
  • the reader can be a system as described herein.
  • the reader can be a bench-top or desk-top system and can be capable of reading a plurality of different devices as described herein.
  • the reader or system is capable of carrying out a chemical reaction and detecting or reading the results of the chemical reaction.
  • a reader is automated according to a protocol sent from an external device (for example, a server comprising a user interface).
  • a reader can also send the results of the detection of the chemical reaction to the server and user interface.
  • the user for example, medical personnel such as a physician or researcher
  • Results can also be stored locally (on the reader) or on the server system.
  • the server can also host patient records, a patient diary, and patient population databases.
  • Figure 8 illustrates the process flow of building a system for assessing the medical condition of a subject.
  • the patient inputs personal data and or measurements from a device, reader, and/or system as described herein into a database as may be present on a server as described.
  • the system can configured to display the personal data on a patient station display.
  • the patient station display is interactive and the patient can modify inputted data.
  • the same or a different database contains data from other subjects with a similar medical condition. Data from the other subjects can be historical data from public or private institutions. Data from other subjects may also be internal data from a clinical study.
  • Figure 8 also illustrates the flow of data from reader collection data that includes the data from the subject to a server that is connected over a public network.
  • the server can manipulate the data or can just provide the data to a user station.
  • the patient data may also be input to the server separately from the data pertaining to a medical condition that is stored in a database.
  • Figure 8 also demonstrates a user station display and the flow of information to medical personnel or a user.
  • a patient at home can input a bodily fluid sample into a cartridge of the invention as described herein and place it in a system or reader as described herein.
  • the patient can view the data from the system at a patient station display and/or modify or input new data into the process flow.
  • the data from the patient can then travel over a public network, such as the internet, for example, in an encrypted format, to a server comprising a network interface and a processor, wherein the server is located at a central computing hub or in a clinical trial center.
  • the server can use medical condition data to manipulate and understand the data from the user and then send the results over a public network as described to a user station.
  • the user station can be in a medical office or laboratory and have a user station display to display the results of the assay and manipulation of the patient data to the medical personnel.
  • the medical personnel can receive results and analysis of a sample from a patient from a test that the patient administered in an alternate location such as the patient's home.
  • Other embodiments and example of systems and components of systems are described herein.
  • the external device can be a computer system, server, or other electronic device capable of storing information or processing information.
  • the external device includes one or more computer systems, servers, or other electronic devices capable of storing information or processing information.
  • an external device may include a database of patient information, for example but not limited to, medical records or patient history, clinical trial records, or preclinical trial records.
  • An external device can store protocols to be run on a system which can be transmitted to the communication assembly of a system when it has received an identifier indicating which device has been inserted in the system.
  • a protocol can be dependent on a device identifier.
  • the external device stores more than one protocol for each device.
  • patient information on the external device includes more than one protocol.
  • the external server stores mathematical algorithms to process a photon count sent from a communication assembly and in some embodiments to calculate the analyte concentration in a bodily fluid sample.
  • the external device can include one or more servers as are known in the art and commercially available. Such servers can provide load balancing, task management, and backup capacity in the event of failure of one or more of the servers or other components of the external device, to improve the availability of the server.
  • a server can also be implemented on a distributed network of storage and processor units, as known in the art, wherein the data processing according to the present invention reside on workstations such as computers, thereby eliminating the need for a server.
  • a server can includes a database and system processes.
  • a database can reside within the server, or it can reside on another server system that is accessible to the server. As the information in a database may contains sensitive information, a security system can be implemented that prevents unauthorized users from gaining access to the database.
  • One advantage of some of the features described herein is that information can be transmitted from the external device back to not only the reader assembly, but to other parties or other external devices, for example without limitation, a PDA or cell phone. Such communication can be accomplished via a wireless network as disclosed herein. In some embodiments a calculated analyte concentration or other patient information can be sent to, for example but not limited to, medical personnel or the patient.
  • the data generated with the use of the subject devices and systems can be utilized for performing a trend analysis on the concentration of an analyte in a subject.
  • assay results can be substantially immediately communicated to any third party that may benefit from obtaining the results. For example, once the analyte concentration is determined at the external device, it can be transmitted to a patient or medical personnel who may need to take further action.
  • the communication step to a third party can be performed wirelessly as described herein, and by transmitting the data to a third party's hand held device, the third party can be notified of the assay results virtually anytime and anywhere.
  • a patient may be contacted immediately anywhere if urgent medical action may be required.
  • an external device can store a plurality of protocols associated with the system or associated with a particular patient or group of patients. For example, when the identifier is transmitted to the external device, software on the external device can obtain the identifier. Once obtained, software on the external device, such as a database, can use the identifier to identify protocols stored in the database associated with the identifier. If only one protocol is associated with the identifier, for example, the database can select the protocol and software on the external device can then transmit the protocol to the communication assembly of the system.
  • the ability to use protocols specifically associated with a device allows for any component of a device of the invention to be used with a single system, and thus virtually any analyte of interest can be detected with a single system.
  • multiple protocols may be associated with a single identifier. For example, if it is beneficial to detect from the same patient an analyte once a week, and another analyte twice a week, protocols on the external device associated with the identifier can also each be associated with a different day of the week, so that when the identifier is detected, the software on the external device can select a specific protocol that is associated with the day of the week.
  • a patient may be provided with a plurality of devices to use to detect a variety of analytes.
  • a subject may, for example, use different devices on different days of the week.
  • the software on the external device associating the identifier with a protocol may include a process to compare the current day with the day the device is to be used based on a clinical trial for example. If for example, the two days of the week are not identical, the external device can wirelessly send notification to the subject using any of the methods described herein or known in the art to notify them that an incorrect device is in the system and also of the correct device to use that day. This example is only illustrative and can easily be extended to, for example, notifying a subject that a device is not being used at the correct time of day.
  • the system can also use a networking method of assessing the medical condition of a subject.
  • a system of communicating information may or may not include a reader for reading subject data. For example, if biomarker data is acquired by a microfluidic point-of-care device, the values assigned to different individual biomarkers may be read by the device itself or a separate device.
  • a reader would be a bar code system to scan in subject data that has been entered in an electronic medical record or a physician chart.
  • a further example of a reader would consist of an electronic patient record database from which subject data could be directly obtained via the communications network. In this way, the efficacy of particular drugs can be demonstrated in real-time, thus justifying reimbursement of the therapy.
  • Noncompliance with a medical treatment can seriously undermine the efficacy of the treatment or trial.
  • the system of the present invention can be used to monitor patient compliance and notify the patient or other medical personnel of such noncompliance.
  • a patient taking a pharmaceutical agent as part of medical treatment plan can take a bodily fluid sample which is assayed as described herein, but a metabolite concentration, for example, detected by the system may be at an elevated level compared to a known profile that will indicate multiple doses of the pharmaceutical agent have been taken.
  • the patient or medical personnel may be notified of such noncompliance via any or the wireless methods discussed herein, including without limitation notification via a handheld device such a PDA or cell phone.
  • a known profile may be located or stored on an external device described herein.
  • the system can be used to identify sub-populations of patients which are benefited or harmed by a therapy. In this way, drugs with varying toxicity that would otherwise be forced from the market can be saved by allocating them only to those who will benefit.
  • the devices and methods of the invention provide an effective means for real-time detection of analytes present in a bodily fluid from a subject.
  • the detection methods may be used in a wide variety of circumstances including identification and quantification of analytes that are associated with specific biological processes, physiological conditions, disorders, stages of disorders or stages of therapy.
  • the devices and methods have a broad spectrum of utility in, for example, drug screening, disease diagnosis, phylogenetic classification, parental and forensic identification, disease onset and recurrence, individual response to treatment versus population bases, and monitoring of therapy.
  • the devices and methods are also particularly useful for advancing preclinical and clinical stage of development of therapeutics, improving patient compliance, monitoring ADRs associated with a prescribed drug, individualized medicine, outsourcing blood testing from the central laboratory to the residence of the patient.
  • the device can be employed on a prescription basis, utilized by pharmaceutical companies for monitoring therapeutic agents following regulatory approval or utilized for payors outsourcing blood tests from a central lab.
  • the present invention provides a method of detecting an analyte in a bodily fluid sample comprising providing a blood sample to a device or system of the invention, allowing the sample to react within at least one assay unit of the device, and detecting the detectable signal generated from the analyte in the blood sample.
  • Figure 1 demonstrates an exemplary embodiment of a device of the invention comprising at least one assay unit and at least one reagent unit.
  • the assay units (for example, designated as sample tips and calibrator tips in Figure 1 ) can contain a capture surface and the reagent units can contain items such as conjugates, washes, and substrates.
  • the device exemplified in Figure 1 also comprises a whole blood sample collection tip, a plasma sample collection tip, a blood input well, a beads well or plasma separation well, a tip touch-off or blotting pad, a dilution well, a diluted plasma sample well or plasma diluent well, collection tip disposal areas.
  • a method comprises performing an Enzyme-linked Immunosorbent Assay (ELISA).
  • ELISA Enzyme-linked Immunosorbent Assay
  • a sample is provided to a sample collection unit of a device as described herein.
  • the device is then inserted into a system, wherein system detects the type of cartridge or device that is inserted.
  • the system can then communicate with an external device to receive a set of instructions or protocol that allow the system to perform the desired assay or assays of the cartridge.
  • the protocol can be sent to the programmable processor of a fluid transfer device of the system.
  • the fluid transfer device engages a sample tip of the cartridge and picks up a certain volume of the sample from the sample collection unit and moves it to a pretreatment unit where red blood cells are removed.
  • the plasma of the sample can then be aspirated into a plasma tip or any assay tip by the fluid transfer device according to the protocol.
  • the tip containing the plasma can then pick up a diluent to dilute the sample as is necessary for the assays to be run.
  • Many different dilutions can be carried by using serial dilutions of the sample.
  • each assay tip or assay unit can contain a sample of a different dilution.
  • the assay unit can then be incubated with the sample to allow any target analyte present to attach to the capture surface.
  • Incubations as described in this example can be at the system or room temperature for any period of time, for example 10 minutes, or can in a heating device of the system as described herein.
  • the assay unit can engage a reagent unit addressed with a reagent corresponding to the assay to be run in each individual assay unit that have a capture surface for that assay.
  • the first reagent is a detector solution of an ELISA, for example, comprising a detector antibody such as a labeled anti-protein antibody different than the capture surface.
  • the detector solution is then aspirated out of the assay unit and then a wash solution can be aspirated into the assay unit to remove any excess detector solution. Multiple wash steps can be used.
  • the final reagent to be added is an enzymatic substrate which causes the bound detector solution to chemiluminesce.
  • the enzymatic substrate is then expelled from the assay unit and the results of the assay are read by a detector of the system.
  • incubations can occur as necessary as described herein. In this example, the entire process after putting the cartridge into the system is automated and carried out by a protocol or set of instructions to the programmable system.
  • One exemplary method proceeds with delivering a blood sample into the blood input well.
  • the sample can then be picked up by a collection tip and inserted into the plasma separation well.
  • the blood can be deposited directly into a well containing a blood separator.
  • plasma separation can be carried out by a variety of methods as described herein.
  • plasma separation proceeds using magnetizable beads and antibodies to remove the components of the blood that are not plasma.
  • the plasma can then be carried by a plasma collection tip as to not contaminate the sample with the whole blood collection tip.
  • the plasma collection tip can pick-up a predetermined amount of diluent and dilute the plasma sample.
  • the diluted plasma sample is then distributed to the assay units (sample tips) to bind to a capture surface.
  • the assay units can be incubated to allow for a capture reaction to be carried out.
  • the assay unit then can be used to collect a conjugate to bind with the reaction in the assay unit.
  • the conjugate can comprise an entity that allows for the detection of an analyte of interest by a detector, such as an optical detector.
  • the reaction can be incubated.
  • a reagent unit containing a wash for the conjugate is then accessed by the assay unit (sample tip) to remove any excess conjugate that can interfere with any analyte detection.
  • a substrate can be added to the assay unit for detection.
  • a calibrator tip assay unit can be used to carry out all of the methods described in this paragraph except the collection and distribution of the sample. Detection and measurements using the calibrator tip assay unit can be used to calibrate the detection and measurements of the analyte from the sample. Other processes and methods similar to those used in this example are described hereinafter.
  • the input well or sample collection unit in the example of Figure 1 can collect of contain any type of commonly employed bodily fluids that include, but are not limited to blood, serum, saliva, urine, gastric and digestive fluid, tears, stool, semen, vaginal fluid, interstitial fluids derived from tumorous tissue liquids extracted from tissue samples, and cerebrospinal fluid.
  • the bodily fluid is blood and can be obtained by a fingerstick.
  • the bodily fluid sample is a blood plasma sample.
  • a bodily fluid may be drawn from a patient and distributed to the device in a variety of ways including, but not limited to, lancing, injection, or pipetting.
  • a lancet punctures the skin and delivers the sample into the device using, for example, gravity, capillary action, aspiration, or vacuum force.
  • the lancet may onboard the device, or part of a reader assembly, or a stand alone component. Where needed, the lancet may be activated by a variety of mechanical, electrical, electromechanical, or any other known activation mechanism or any combination of such methods.
  • a patient can simply provide a bodily fluid to the device, as could occur, for example, with a saliva sample.
  • the collected fluid can be placed into a collection well or unit of the device.
  • the volume of bodily fluid to be used with a method or device described herein is generally less than about 500 microliters, further can be between about 1 to 100 microliters.
  • a sample of 1 to 50 microliters, 1 to 40 microliters, 1 to 30 microliters, 1 to 10 microliters or even 1 to 3 microliters can be used for detecting an analyte using the subject fluidic device.
  • the sample is 20 microliters.
  • the volume of bodily fluid used for detecting an analyte utilizing the devices, systems, or methods is one drop of fluid.
  • one drop of blood from a pricked finger can provide the sample of bodily fluid to be analyzed with a device, system, or method of the invention.
  • the bodily fluids are used directly for detecting the analytes present in the bodily fluid without further processing.
  • the bodily fluids can be pre-treated before performing the analysis with a device.
  • the choice of pre-treatments will depend on the type of bodily fluid used and/or the nature of the analyte under investigation. For instance, where the analyte is present at low level in a sample of bodily fluid, the sample can be concentrated via any conventional means to enrich the analyte. Methods of concentrating an analyte include but are not limited to drying, evaporation, centrifugation, sedimentation, precipitation, and amplification.
  • analyte is a nucleic acid
  • it can be extracted using various lytic enzymes or chemical solutions or using nucleic acid binding resins following the accompanying instructions provided by manufacturers.
  • extraction can be performed using lysing agents including but not limited to anticoagulants such as EDTA or heparin, denaturing detergent such as SDS or non-denaturing detergent such as Thesit, sodium deoxylate, triton X-100, and tween-20.
  • the subject collects a sample of bodily fluid with a syringe.
  • the sample can enter the syringe through a capillary tube.
  • the subject performs a fmgerstick and touches the outer end of the glass capillary to the blood so that blood is drawn by capillary action and fills the capillary with a volume.
  • the sample volume is known.
  • the sample volume is in the range of about 5 - 20 microliters or other volume ranges as described herein.
  • a method and system is provided to obtain a plasma sample substantially free of red blood cells from a blood sample.
  • the analytes are often contained in the blood plasma, and the red blood cells can interfere with a reaction.
  • the analytes of interest are in the serum or plasma.
  • the final reported concentration of multiple blood tests often needs to relate to the concentration of blood serum or blood plasma in a diluted sample.
  • blood serum or blood plasma is the test medium of choice in the lab. Two operations may be necessary prior to running an assay, dilution and red blood cell removal.
  • Blood samples vary significantly in the proportion of the sample volume occupied by red cells (the hematocrit which varies from about 20 - 60%).
  • the volume of sample obtained may not be that which is intended. If a change in volume is not recognized, it can lead to error in the reported analyte concentrations.
  • the present invention provides a method of retrieving plasma from a blood sample that comprises mixing a blood sample in the presence of magnetizable particles in a sample collection unit, wherein the magnetizable particles comprise an antibody capture surface for binding to non-plasma portions of the blood sample, and applying a magnetic field above a plasma collection area to the mixed blood sample to effect suspension of the non-plasma portions of the blood sample on top of the plasma collection area, thereby retrieving the plasma from a blood sample.
  • the device or system of the invention may include a magnetic reagent or object which binds to red cells and enables magnetic removal of red cells from plasma.
  • the reagent can be provided in lyophilized form but also can be present as a liquid dispersion.
  • a reagent comprised of magnetizable particles (for example, about 1 micrometer in size) can be coated with an antibody to a red cell antigen or to some adaptor molecule.
  • the reagent also contains unbound antibodies to red cell surface antigens, which may be unlabeled or labeled with an adaptor moiety (such as biotin, digoxigenin, or fluorescein).
  • the red blood cells in a diluted sample co-agglutinate with the magnetizable particles aided by a solution phase antibody.
  • a lectin that recognizes a red cell surface carbohydrate can be used as a co-agglutination agent.
  • combinations of red cell agglutinating agents are used.
  • a device of the invention can comprise a blood filter, such as a pad of glass fiber, to aid in the separation of red blood cells from a sample.
  • a co-agglutination can occur in which many, if not all, of the red cells form a mixed agglutinate with the magnetizable particles.
  • the reagent dissolution and mixing process is driven by repeated aspiration using a tip or collection tip of the invention or a pipette-like tip.
  • the mass can be separated from the blood plasma by use of a magnet to hold the mass in place as plasma is allowed to exit the tip.
  • the plasma exits the tip by gravity in a vertical orientation, while the magnet holds the mass in place.
  • the plasma exits the tip by vacuum or pressure means, while the mass is held within the tip.
  • the plasma can be deposited into a well, another collection tip, or assay unit of the invention.
  • FIGS 9A through 9E An example of a plasma separation method of the invention is demonstrated in Figures 9A through 9E .
  • a whole blood sample 901 has been aspirated into a sample tip 910 as described herein, for example in the amount of about 20 microliters.
  • the whole blood sample 901 is then deposited into a separation well 920 (for example, a well containing magnetic beads or particles) of an example device.
  • Figure 9B illustrates a method of suspending and mixing a magnetic reagent in the whole blood sample 902 in a separation well (for example, magnetic bead particles and free binding molecules).
  • Figure 9C demonstrates a 10 microliter air slug 930 that can be used to prevent loss from the tip 910 .
  • the mixed whole blood sample and magnetic reagent 902 are incubated for several seconds (for example, 60 to 180 seconds) to allow an agglutination reaction to occur.
  • Figure 9D demonstrates the application of a magnetic field 940 to the whole blood cell and magnetic reagent mixture 902 .
  • the magnetic field 940 can be applied by a magnetic collar 942 that is incorporated with a system or with any magnetic means known in the art.
  • the magnetic field 940 attracts any particles that have adhered to the magnetic reagent. In this way, the plasma 903 , which does not adhere with the magnetic reagent, can be separated from non-plasma portions of a whole blood sample.
  • Figure 9E demonstrates a method of distributing a blood plasma sample 903 , as separated by the magnetic reagent described herein, into a well or unit 950 of a device as described herein.
  • the blood plasma sample 903 can also be distributed to a collection tip or assay unit, as well as any other sort of assay device as obvious to one skilled in the art.
  • the magnetic field 940 is shown to move with the tip 910 distributing the blood plasma sample 903.
  • 5 to 8 microliters of plasma have been removed from a 20 microliter whole blood sample.
  • 1 to 99% of a whole blood sample can be plasma separated using a method of the invention.
  • 25 to 60% of the volume of the whole blood sample is plasma that can be separated.
  • a capillary plasma collection tip (which can be operated by a robotic system or any other system of the invention) collects the blood plasma sample by capillary and aspiration force.
  • Another step can comprise distributing the plasma sample in a diluent, and the sample can then be diluted by the diluent.
  • the diluted blood plasma sample can then be collected by the collection tip in a predetermined volume.
  • the diluted blood plasma sample can then be mixed and distributed into a well or unit of a device to be distributed to one or a plurality of assay units of a device of the invention.
  • the sample can also be distributed into any other type of device, such as a microtiter plate, as would be obvious to those skilled in the art.
  • a fluid transfer tip can contain the agglutinated mass and the plasma could be deposited into a microtiter plate.
  • Other devices and systems as would be obvious to those skilled in the art could be utilized to execute the example blood plasma separation as disclosed herein.
  • the sample of bodily fluid can also be diluted in a variety of other manners, such as using a sample collection device capable of dilution.
  • the housing of the sample collection device can comprise a tube.
  • two moveable seals can contain a volume of a diluent.
  • the volume of the diluent is predetermined, e.g., in about the range of 50 microliters to 1 milliliter, preferably in the range of about 100 microliters to 500 microliters.
  • a method for automated detection of a plurality of analytes in a bodily fluid sample comprises: providing the bodily fluid sample to a fluidic device, wherein the fluidic device comprises: a sample collection unit configured to contain the bodily fluid sample; an array of assay units, wherein an individual assay unit of said array of assay units is configured to run a chemical reaction that yields a signal indicative of an individual analyte of said plurality of analytes being detected; and an array of reagent units, wherein an individual reagent unit of said array of reagent units contains a reagent.
  • the method can also comprise engaging the individual assay unit using a fluid transfer device.
  • bodily fluid sample can be transferred from the sample collection unit to the individual assay unit using the fluid transfer device and the reagent from the individual reagent unit can be transferred to the individual assay unit, thereby reacting the reagent with the bodily fluid sample to yield the signal indicative of the individual analyte of the plurality of analytes being detected.
  • the fluid transfer device comprises a plurality of heads, wherein an individual head of the plurality of heads is configured to engage the individual assay unit; and wherein said fluid transfer device comprises a programmable processor configured to direct fluid transfer of the bodily fluid sample from the sample collection unit and the reagent from the individual reagent unit into the individual assay unit.
  • instructions are provided to the programmable processor, for example, by a user, a subject, or the manufacturer. Instructions can be provided from an external device, such as a personal electronic device or a server.
  • the instructions can direct the step of transferring the bodily fluid sample to the individual assay unit.
  • the step of transferring the bodily fluid sample can affect a degree of dilution of the bodily fluid sample in the individual assay unit to bring the signal indicative the individual analyte of the plurality of analytes being detected within a detectable range.
  • the degree of dilution of the bodily fluid sample brings the signals indicative of the at least two individual analytes within a detectable range as described herein.
  • Pattern recognition techniques can be used to determine if the detection of an analyte or a plurality of analytes by a method as described herein is within or outside a certain range. For example, detectable signals outside the reportable range can be rejected.
  • the certain range can be established during calibration of a fluidic device the reagent and assay units. For example, the range is established when a device is assembled in a just-in-time fashion.
  • the detectable signal of an analyte as detected with a lower dilution factor or degree of dilution exceeds that for a higher dilution factor, the lower dilution result can be rejected as invalid.
  • concentrations of an analyte in a sample as derived from signals from samples with different degrees of dilution get lower as the degree of dilution becomes greater. If this does happen, an assay result can be verified.
  • the systems, devices, and methods herein provide the flexibility of quality control rules such as those described that many POC devices cannot offer.
  • the systems, devices, and methods provide many of the quality control features as would be expected in a laboratory setting.
  • a sample is diluted in a ratio that is satisfactory for both high senstivity and low sensitivity assays.
  • a dilution ratio of sample to diluent can be in the range of about 1:10,000 - 1:1.
  • the device can enable a sample to be diluted into separate locations or extents.
  • the device can also enable the sample to be subject to serial dilutions.
  • serial dilution within the device or system can dilute the sample up to 10,000,000,000:1.
  • a sample containing an analyte for detection can be moved from a first location to a second location by aspiration-, syringe-, or pipette-type action.
  • the sample can be drawn into the reaction tip by capillary action or reduced atmospheric pressure.
  • the sample is moved to many locations, including an array of assay units of a device of the invention and different wells in the housing of a device of the invention.
  • the process of moving the sample can be automated by a system of the invention, as described herein.
  • the assay units and/or collection tips containing the sample can also be moved from a first location to a second location.
  • the process of moving an assay unit or a collection tip can be automated and carried out by a user-defined protocol.
  • the assay units are moved to collect reagent from a reagent unit of the invention.
  • movement of an assay unit is automated.
  • Aspiration-, syringe-, or pipette-type action can be used to collect reagent from a reagent unit into an assay unit.
  • the entire unit can be incubated for a period of time to allow for a reaction between the sample and the capture surface of the assay unit.
  • the amount of time needed to incubate the reaction is often dependent on the type of assay being run.
  • the process can be automated by a system of the invention. In an embodiment, the incubation time is between 30 seconds and 60 minutes. In another embodiment, the incubation time is 10 minutes.
  • An assay unit can also be incubated at an elevated temperature.
  • the assay unit is incubated at temperature in a range of about 20 to 70 degrees Celsius.
  • the assay unit can be inserted into a heating block to elevate the temperature of the assay unit and/or the contents of the assay unit.
  • a conjugate is added to the assay unit after a sample has been added to the unit.
  • the conjugate can contain a molecule for labeling an analyte captured by a capture surface in the assay unit. Examples of conjugates and capture surface are described hereinafter.
  • the conjugate can be a reagent contained within a reagent unit.
  • the conjugate can be distributed to the assay unit by aspiration-, syringe-, or pipette-type action.
  • the assay unit can be incubated to allow the conjugate to react with an analyte within the assay unit.
  • the incubation time can be determined by the type of assay or the analyte to be detected.
  • the incubation temperature can be any temperature appropriate for the reaction.
  • a device can comprise an array of addressable assay units configured to run a chemical reaction that yields a detectable signal indicative of the presence or absence of the analyte, and an array of addressable reagent units, each of which is addressed to correspond to one or more addressable assay units in said device, such that individual reagent units are calibrated in reference to the corresponding assay unit(s) before the arrays are assembled on the device.
  • the device is calibrated by calibrating the assay units and reagent units before they are assembled on the device. The device can then be assembled using the calibrated components, making the device, and a method and system that utilize the device, modular components.
  • Calibration can be pre-established by measuring the performance of assay reagents, such as conjugates, before the assay units and reagent unit are assembled in a device of the invention.
  • Calibration information and algorithms can be stored on a server linked wirelessly to the assay system. Calibration can be performed in advance or retrospectively by assays performed in replicate systems at a separate location or by using information obtained when the assay system is used.
  • a control material can be used in a device or system to measure or verify the extent of dilution of a bodily fluid sample.
  • solid-phase based assays such as ELISA
  • an assay uses a solid-phase reagent that is difficult to quality control without destruction of its function.
  • the systems and methods herein provide methods to determine the dilution achieved in a POC system using a disposable device with automated mixing and/or dilution.
  • a method provides retrospective analysis, for example, by use of a server in real time to analyze data prior to reporting results.
  • an assay can be performed and a control assay can be run in parallel to the assay.
  • the control assay provides a measurement of an expected dilution of the sample.
  • the control assay can verify the dilution of the sample and thus, dilution of a sample for the assay or plurality of assays run within the system can be considered accurate.
  • a method of measuring a volume of a liquid sample can comprise: reacting a known quantity of a control analyte in a liquid sample with a reagent to yield a detectable signal indicative of the control analyte; and comparing an intensity of said detectable signal with an expected intensity of said detectable signal, wherein the expected intensity of said signal is indicative of an expected volume of the liquid sample, and wherein said comparison provides a measurement of said volume of said liquid sample being measured.
  • the control analyte is not present in said liquid sample in a detectable amount.
  • a method can further comprise verifying the volume of said liquid sample when the measurement of the volume of the sample is within about 50% of the expected volume of the liquid sample.
  • a method utilized a device or system described herein can further comprise: reacting a bodily fluid sample containing a target analyte with a reagent to yield a detectable signal indicative of the target analyte; and measuring the quantity of the target analyte in the bodily fluid sample using an intensity of said detectable signal indicative of the target analyte and the measurement of said volume of said liquid sample.
  • the liquid sample and the bodily fluid sample can be the same sample.
  • the control analyte does not react with the target analyte in the bodily fluid sample, therefore providing not interacting with detection of the target analyte.
  • the liquid sample and the bodily fluid sample are different liquid samples.
  • a control liquid such as water
  • a blood sample or in another example, a saliva sample and a blood sample.
  • a control analyte can be, without limitation, fluorescein-labeled albumin, fluorescein labeled IgG, anti-fluorescein, anti-digoxigenin, digoxigenin-labeled albumin, digoxigenin-labeled IgG, biotinylated proteins, non-human IgG.
  • Other exemplary control analytes can be obvious to one skilled in the art.
  • the control analyte does not occur in a human bodily fluid sample.
  • a POC system configured to detect a plurality of analytes within a sample
  • the system can have capabilities to dilute and mix liquids.
  • an automated system or user can use a control assay to measure the dilution actually achieved and factor that dilution into the system calibration.
  • a control analyte can be never found in the sample of interest and dried into a reagent unit.
  • the quantity of the dried control analyte can be known and mixed with a sample in the reagent unit.
  • the concentration of analyte can be measured to indicate the volume of sample and any dilution performed on the sample.
  • control analytes for an immunoassay include, but are not limited to: fluorescein-labeled protein, biotinylated protein, fluorescein-labeled, AxlexaTM-labeled, Rhodamine-labeled, Texas Red-labeled, immunoglobulin.
  • the labeling can be achieved by having at least two haptens linked per molecule of protein. In some embodiments, 1-20 haptens are linked per molecule of protein. In a further embodiment, 4-10 haptens are linked per molecule of protein. Many proteins have large numbers of free amino groups to which the haptens can be attached. In many instances, hapten-modified proteins are stable and soluble.
  • haptens such as fluorescein and Texas Red are sufficiently large and rigid that antibodies with high affinity can be made (for example, a hapten is large enough to fill the antibody binding site).
  • haptens can be attached to proteins using reagents, such as fluorescein isothocyanate, and fluorescein carboxylic acid NHS ester to create control analytes in which the part recognized by the assay system is the hapten.
  • a method utilizes dried control analyte.
  • a dried control analyte avoids dilution of the sample and can make the control analyte more stable.
  • Dried control analyte can be formulated so it dissolves rapidly and/or completely on exposure to a liquid sample.
  • a control analyte can be an analyte for which antibodies with high affinity.
  • a control analyte can be an analyte that has no cross reaction with any endogenous sample component. Additionally, for example, the analyte can be inexpensive and/or easy to make.
  • the control analyte is stable over the lifetime of the device or system described herein.
  • Exemplary carriers used to create analytes with covalently linked haptens include proteins such as, but not limited to: albumin, IgG, and casein.
  • Exemplary polymer carriers used to create novel analytes with covalently linked haptens include, but are not limited to: Dextran, Poly-vinylpyrolidone.
  • Exemplary excipients used to formulate and stabilize control analytes include, but are not limited to: sucrose, salts, and buffers (such as sodium phosphate and tris chloride).
  • a control analyte and method as described herein can be used in a variety of ways including the examples described herein.
  • a method can measure a volume of a sample.
  • a method measures dilution or a dilution factor or a degree of dilution of a sample.
  • a method provides a concentration of the control analyte in a sample.
  • measurements from a method herein using a control analyte can be used to verify or describe measurements of target analytes.
  • a fluid transfer device with multiple heads may be used to distribute liquid into a plurality of assay units, including a control unit.
  • liquid amount distributed into the plurality of units is the same or similar between the individual units.
  • a method described herein with a control analyte can be used to verify that the correct volume of sample has been collected or utilized within a device or system.
  • a method verifies the correct volume of diluent has been provided to the sample.
  • the dilution factor or degree of dilution can also be verified.
  • a method with a control analyte verifies the correct volume of diluted sample has been distributed to the plurality of units.
  • Figure 10 demonstrates an exemplary method of a control assay as described herein comprising a known quantity of control analyte.
  • a unit 1010 before assembly into a cartridge can be filled with a solution 1001 comprising a known mass of control analyte 1002.
  • the liquid of the solution can be removed and the unit 1010 dried to leave the control analyte 1002 in the unit 1010 .
  • the unit 1010 can then be inserted into a device and transported for use.
  • the unit 1010 is used and receives a sample or diluent 1003
  • the sample 1003 can be delivered in an expected volume and mixed with the dried control analyte 1002 within the unit 1010 to create a control solution 1004 with an expected concentration.
  • the control solution 1004 can be optionally diluted.
  • the control analyte 1002 can be detected by the same manners as a target analyte in the device.
  • the control analyte concentration in the control solution 1004 is measured.
  • the measurement of the concentration can be used to calculate the volume of the sample 1003 added to create the control solution 1004 . In this manner, a user can compare the measured volume of the sample 1003 with the expected volume of the sample 1003 .
  • red blood cells can be removed from a blood sample. However, if some red blood cells remain, or red blood cells are not removed from a blood sample, a method with a control analyte can be used to correct for effects from red blood cells in the blood sample. Because hematocrit can vary significantly (for example, from 20 - 60% of the total volume of a sample), the quantity of an analyte in a fixed or expected volume (v) of blood can be a function of the hematocrit (H expressed here as a decimal fraction). For example, the quantity of analyte with a concentration C in plasma is C*v*(1-H).
  • undiluted blood can be dispensed into a device as described and red cells can be removed.
  • a control analyte concentration in the plasma fraction can then be measured to estimate the volume of sample plasma and determine the hematocrit.
  • unbound conjugate may need to be washed from a reaction site to prevent unbound conjugates from producing inaccurate detection.
  • the limiting step of many immunoassays is a washing step. The compromise of minimum carryover and high sensitivity is dependent on the wash removal of unbound conjugate.
  • the wash step can be severely limited in a microtiter plate format due to the difficulty of removing the wash liquid from a well (for example, by automatic means).
  • An assay unit device and system of the invention can have a number of advantages in the way liquids are handled. An advantage may be an improvement in the signal to noise ratio of an assay.
  • a wash of the conjugate can occur by either pushing the wash solution from above or drawing the wash solution up and expelling the liquid similar to the loading of the sample.
  • the washing can be repeated as many times as necessary.
  • the device can store the wash buffer in reagent units and the assay unit can be brought into fluid communication with the wash.
  • the wash reagent is able to remove unbound reagent from the assay units by about 99, 99.9, or 99.999% by washing.
  • Washing efficiency is typically defined by the ratio of signal from a given assay to the total amount of signal generated by an assay with no wash step and can be readily determined by routine experimentation. It can be generally preferred to increase the volume of washing solution and time of incubation but without sacrificing the signals from a given assay.
  • washing is performed with about 50 ul to about 5000 ul of washing buffer, preferably between about 50 ul to about 500 ul washing buffer, for about 10 to about 300 seconds.
  • the last step is to distribute an enzymatic substrate to detect the conjugate by optical or electrical means. Examples of substrates are described hereinafter.
  • the reagent in the individual reagent unit of a device herein can be an enzyme substrate for an immunoassay.
  • the step of transferring the substrate reagent from the individual reagent unit can be repeated after a reaction at the capture site.
  • enzymatic substrate is transferred to a reaction site and incubated.
  • used substrate can be removed and replaced with fresh substrate and the assay signal remeasured.
  • a signal indicative of the individual analyte being can be detected using a system as described herein from both the first and the second application of substrate.
  • the second substrate is usually the same as the original substrate.
  • the second substrate is transferred to a reaction site from a second reagent unit of a device herein.
  • the second substrate is transferred to a reaction site from the same reagent unit as the original substrate. Transferring a second substrate thereby creates a second reaction to yield a second signal indicative of the individual analyte.
  • the intensity of the original signal and a second intensity of the second signal can be compared to calculate the final intensity of the signal indicative of the individual analyte and whether the assay was properly conducted.
  • the intensities of the multiple signals can be used for quality control of an assay. For example, if the signals differ by 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100% or more, the assay results may be disregarded.
  • a method as described herein comprises re-loading sample and or detector-conjugate (enzyme-labeled antibody) and or the enzyme substrate and sample to rectify or confirm an assay signal or to use as an internal control.
  • re-use of an assay tip or unit as described can be provided to verify function and/or to add further sample or control materials obtain a second signal.
  • a method of re-loading a substrate to an enzyme unit is enabled by the ability of a system as described herein to automatically to transfer liquid samples and reagents into the assay units.
  • Some assays do not require the system to deliver a result immediately or on a schedule, therefore, a control method as described offers an opportunity to possibly enhance the reliability of the results.
  • a response observed following iterations of adding an enzyme substrate can be used to verify the initial response or to calculate spike recovery.
  • a control method provides replicate analyses using an assay unit gave a response significantly lower than that expected.
  • exemplary assay errors include, but are not limited to, improper manufacturing of an assay unit or device, improper aspiration of a sample and/or one or more reagents, an assay unit is not positioned properly relative to the photomultiplier during detection, and a missing assay unit in the device or system.
  • the present invention provides a method of obtaining pharmacological data useful for assessing efficacy and/or toxicity of a pharmaceutical agent from a test animal utilizing the subject fluidic devices or systems.
  • the total blood volume in a mouse is 6-8 mL of blood per 100 gram of body weight.
  • a benefit of the current invention is that only a very small volume of blood is required to perform preclinical trials on mice or other small laboratory animals. In some embodiments between about 1 microliter and about 50 microliters are drawn. In an embodiment between about 1 microliter and 10 microliters are drawn. In preferred embodiments about 5 microliters of blood are drawn.
  • a further advantage of keeping the test animal alive is evident in a preclinical time course study.
  • multiple mice for example, are used to monitor the levels of an analyte in a test subject's bodily fluid over time, the added variable of using multiple subjects is introduced into the trial.
  • a single test animal can be used as its own control over a course of time, a more accurate and beneficial preclinical trial can be performed.
  • a method of automatically monitoring patient compliance with a medical treatment using the subject devices or systems comprises the steps of allowing a sample of bodily fluid to react with assay reagents in a device to yield a detectable signal indicative of the presence of an analyte in said sample; detecting said signal with said device; comparing said signal with a known profile associated with said medical treatment to determine if said patient is compliant or noncompliant with said medical treatment; and notifying a patient of said compliance or noncompliance.
  • system and methods of the invention provide a means of discovering new biomarkers and/or validating by association of trends in such markers with disease and therapy outcomes.
  • system and methods of the invention can identify trends in biomarker levels and daily patient diary information over time that can be used to adjust a drug dose to an optimal level for particular patients (for example, adaptive dose-ranging).
  • noncompliance may include taking an improper dose of a pharmaceutical agent including without limitation multiple doses or no dose, or may include inappropriately mixing pharmaceutical agents.
  • a patient is notified substantially immediately after the signal is compared with a known profile.
  • a method of alerting a patient to test a sample of bodily fluid using a device as described herein comprises providing a protocol to be run on said device, said protocol located on an external device, associated with said patient, and comprising a time and date to test said sample of bodily fluid; and notifying patient to test said bodily fluid on said date and time if said sample has not been tested.
  • a patient can be notified wirelessly as described herein. Compliance with therapeutic regimes can be improved by use of prompts on a display and obtaining responses from patients (for example, by way of a touch-screen).
  • a patient may be provided with a device when procuring a prescription of drugs by any common methods, for example, at a pharmacy.
  • a clinical trial subject may be provided with such devices when starting a clinical trial.
  • the patient or subject's contact information including without limitation cell phone, email address, text messaging address, or other means of wireless communication, may at that time be entered into the external device and associated with the patient or subject as described herein, for example, in a database.
  • Software on the external device may include a script or other program that can detect when a signal generated from a detection device has not yet been sent to the external device, for example at a given time, and the external device can then send an alert notifying the patient to take a bodily fluid sample.
  • the system is provided directly to a consumer and is used in lifestyle and/or athletic management. Relevant lifestyle and exercise data can be input and measurements of parameters indicative of muscle damage, anaerobic metabolism (for example, lactic acid) can be measured. In some embodiments, the system can be sufficiently small to be portable.
  • the system is particularly suited for measurement of markers in the blood of small animals such as rats and mice that are commonly used in pre-clinical work.
  • small animals such as rats and mice that are commonly used in pre-clinical work.
  • Such animals only have a small volume of blood and so assay systems requiring very small volumes of sample are particularly useful, especially in longitudinal studies where several samples from a single animal are needed in rapid succession. These considerations can be especially important when several analytes need to be measured in parallel.
  • the system includes a convenient way to package the several elements required for multiple complex assays in a secure form for shipping. For example, assay elements click fit into a housing.
  • a variety of assays may be performed on a fluidic device according to the present invention to detect an analyte of interest in a sample.
  • labels are detectable by spectroscopic, photochemical, biochemical, electrochemical, immunochemical, or other chemical means.
  • useful nucleic acid labels include the radioisotopes 32P, 35S, fluorescent dyes, electron-dense reagents, enzymes,.
  • a wide variety of labels suitable for labeling biological components are known and are reported extensively in both the scientific and patent literature, and are generally applicable to the present invention for the labeling of biological components.
  • Suitable labels include radionucleotides, enzymes, substrates, cofactors, inhibitors, fluorescent moieties, chemiluminescent moieties, bioluminescent labels, or colorimetric labels.
  • Reagents defining assay specificity optionally include, for example, monoclonal antibodies, polyclonal antibodies, proteins, nucleic acid probes or other polymers such as affinity matrices, carbohydrates or lipids. Detection can proceed by any of a variety of known methods, including spectrophotometric or optical tracking of radioactive, fluorescent, or luminescent markers, or other methods which track a molecule based upon size, charge or affinity.
  • a detectable moiety can be of any material having a detectable physical or chemical property.
  • a label includes without limitation any composition detectable by spectroscopic, photochemical, biochemical, immunochemical, nucleic acid probe-based, electrical, optical thermal, or other chemical means.
  • the label is coupled directly or indirectly to a molecule to be detected such as a product, substrate, or enzyme, according to methods well known in the art.
  • a molecule to be detected such as a product, substrate, or enzyme, according to methods well known in the art.
  • a wide variety of labels are used, with the choice of label depending on the sensitivity required, ease of conjugation of the compound, stability requirements, available instrumentation, and disposal provisions.
  • Non-radioactive labels are often attached by indirect means.
  • a receptor specific to the analyte is linked to a signal generating moiety.
  • the analyte receptor is linked to an adaptor molecule (such as biotin or avidin) and the assay reagent set includes a binding moiety (such as a biotinylated reagent or avidin) that binds to the adaptor and to the analyte.
  • the analyte binds to a specific receptor on the reaction site.
  • a labeled reagent can form a sandwich complex in which the analyte is in the center.
  • the reagent can also compete with the analyte for receptors on the reaction site or bind to vacant receptors on the reaction site not occupied by analyte.
  • the label is either inherently detectable or bound to a signal system, such as a detectable enzyme, a fluorescent compound, a chemiluminescent compound, or a chemiluminogenic entity such as an enzyme with a luminogenic substrate.
  • a signal system such as a detectable enzyme, a fluorescent compound, a chemiluminescent compound, or a chemiluminogenic entity such as an enzyme with a luminogenic substrate.
  • ligands and anti-ligands can be used. Where a ligand has a natural anti-ligand, for example, biotin, thyroxine, digoxigenin, and cortisol, it can be used in conjunction with labeled, anti-ligands. Alternatively, any haptenic or antigenic compound can be used in combination with an antibody.
  • the label can also be conjugated directly to signal generating compounds, for example, by conjugation with an enzyme or fluorophore.
  • Enzymes of interest as labels will primarily be hydrolases, particularly phosphatases, esterases and glycosidases, or oxidoreductases, particularly peroxidases.
  • Fluorescent compounds include fluorescein and its derivatives, rhodamine and its derivatives, dansyl groups, and umbelliferone.
  • Chemiluminescent compounds include dioxetanes, acridinium esters, luciferin, and 2,3-dihydrophthalazinediones, such as luminol.
  • means for detection include scintillation counting or photographic films as in autoradiography.
  • the label may be detected by exciting the fluorochrome with light of an appropriate wavelength and detecting the resulting fluorescence by, for example, microscopy, visual inspection, via photographic film, by the use of electronic detectors such as digital cameras, charge coupled devices (CCDs) or photomultipliers and phototubes, or other detection device.
  • enzymatic labels are detected by providing appropriate substrates for the enzyme and detecting the resulting reaction product.
  • simple colorimetric labels are often detected simply by observing the color associated with the label. For example, conjugated gold often appears pink, while various conjugated beads appear the color of the bead.
  • the detectable signal may be provided by luminescence sources.
  • Luminescence is the term commonly used to refer to the emission of light from a substance for any reason other than a rise in its temperature.
  • atoms or molecules emit photons of electromagnetic energy (e.g ., light) when then move from an excited state to a lower energy state (usually the ground state).
  • exciting cause is a photon
  • the luminescence process is referred to as photoluminescence.
  • the exciting cause is an electron
  • the luminescence process can be referred to as electroluminescence. More specifically, electroluminescence results from the direct injection and removal of electrons to form an electron-hole pair, and subsequent recombination of the electron-hole pair to emit a photon.
  • Luminescence which results from a chemical reaction is usually referred to as chemiluminescence.
  • Luminescence produced by a living organism is usually referred to as bioluminescence.
  • photoluminescence is the result of a spin-allowed transition (e.g ., a single-singlet transition, triplet-triplet transition)
  • the photoluminescence process is usually referred to as fluorescence.
  • fluorescence emissions do not persist after the exciting cause is removed as a result of short-lived excited states which may rapidly relax through such spin-allowed transitions.
  • photoluminescence is the result of a spin-forbidden transition (e.g ., a triplet-singlet transition)
  • the photoluminescence process is usually referred to as phosphorescence.
  • phosphorescence emissions persist long after the exciting cause is removed as a result of long-lived excited states which may relax only through such spin-forbidden transitions.
  • a luminescent label may have any one of the above-described properties
  • Suitable chemiluminescent sources include a compound which becomes electronically excited by a chemical reaction and may then emit light which serves as the detectible signal or donates energy to a fluorescent acceptor.
  • a diverse number of families of compounds have been found to provide chemiluminescence under a variety or conditions.
  • One family of compounds is 2,3-dihydro-1,4-phthalazinedione.
  • a frequently used compound is luminol, which is a 5-amino compound.
  • Other members of the family include the 5-amino-6,7,8-trimethoxy- and the dimethylamino[ca]benz analog. These compounds can be made to luminesce with alkaline hydrogen peroxide or calcium hypochlorite and base.
  • Chemiluminescent analogs include para-dimethylamino and -methoxy substituents. Chemiluminescence may also be obtained with oxalates, usually oxalyl active esters, for example, p-nitrophenyl and a peroxide such as hydrogen peroxide, under basic conditions. Other useful chemiluminescent compounds that are also known include -N-alkyl acridinum esters and dioxetanes. Alternatively, luciferins may be used in conjunction with luciferase or lucigenins to provide bioluminescence.
  • analytes as used herein includes without limitation drugs, prodrugs, pharmaceutical agents, drug metabolites, biomarkers such as expressed proteins and cell markers, antibodies, serum proteins, cholesterol and other metabolites, polysaccharides, nucleic acids, biological analytes, biomarkers, genes, proteins, or hormones, or any combination thereof.
  • Analytes can be combinations of polypeptides, glycoproteins, polysaccharides, lipids, and nucleic acids.
  • biomarkers are associated with a particular disease or with a specific disease stage.
  • Such analytes include but are not limited to those associated with autoimmune diseases, obesity, hypertension, diabetes, neuronal and/or muscular degenerative diseases, cardiac diseases, endocrine disorders, metabolic disorders, inflammation, cardiovascular diseases, sepsis, angiogenesis, cancers, Alzheimer's disease, athletic complications, and any combinations thereof.
  • biomarkers that are present in varying abundance in one or more of the body tissues including heart, liver, prostate, lung, kidney, bone marrow, blood, skin, bladder, brain, muscles, nerves, and selected tissues that are affected by various disease, such as different types of cancer (malignant or non-metastatic), autoimmune diseases, inflammatory or degenerative diseases.
  • body tissues including heart, liver, prostate, lung, kidney, bone marrow, blood, skin, bladder, brain, muscles, nerves, and selected tissues that are affected by various disease, such as different types of cancer (malignant or non-metastatic), autoimmune diseases, inflammatory or degenerative diseases.
  • analytes that are indicative of a microorganism, virus, or Chlamydiaceae.
  • exemplary microorganisms include but are not limited to bacteria, viruses, fungi and protozoa.
  • Analytes that can be detected by the subject method also include blood-born pathogens selected from a non-limiting group that consists of Staphylococcus epidermidis, Escherichia coli, methicillin-resistant Staphylococcus aureus (MSRA), Staphylococcus aureus, Staphylococcus hominis, Enterococcus faecalis, Pseudomonas aeruginosa, Staphylococcus capitis, Staphylococcus warneri, Klebsiella pneumoniae, Haemophilus influenzae, Staphylococcus simulans, Streptococcus pneumoniae and Candida albicans.
  • MSRA methicillin-resistant Staphylococcus aureus
  • Analytes that can be detected by the subject method also encompass a variety of sexually transmitted diseases selected from the following: gonorrhea (Neisseria gorrhoeae), syphilis (Treponena pallidum), clamydia (Clamyda tracomitis), nongonococcal urethritis (Ureaplasm urealyticum), yeast infection (Candida albicans), chancroid (Haemophilus ducreyi), trichomoniasis (Trichomonas vaginalis), genital herpes (HSV type I & II), HIV I, HIV II and hepatitis A, B, C, G, as well as hepatitis caused by TTV.
  • gonorrhea Neisseria gorrhoeae
  • syphilis Teponena pallidum
  • clamydia Clamyda tracomitis
  • Additional analytes that can be detected by the subject methods encompass a diversity of respiratory pathogens including but not limited to Pseudomonas aeruginosa, methicillin-resistant Staphlococccus aureus (MSRA), Klebsiella pneumoniae, Haemophilis influenzae, Staphlococcus aureus, Stenotrophomonas maltophilia, Haemophilis parainfluenzae, Escherichia coli, Enterococcus faecalis, Serratia marcescens, Haemophilis parahaemolyticus, Enterococcus cloacae, Candida albicans, Moraxiella catarrhalis, Streptococcus pneumoniae, Citrobacter freundii, Enterococcus faecium, Klebsella oxytoca, Pseudomonas fluorscens, Neiseria meningitidis, Streptococcus py
  • Theophylline CRP, CKMB, PSA, Myoglobin, CA125, Progesterone, TxB2, 6-keto-PGF-1-alpha, and Theophylline, Estradiol , Lutenizing hormone, Triglycerides, Tryptase, Low density lipoprotein Cholesterol, High density lipoprotein Cholesterol, Cholesterol, IGFR.
  • liver markers include without limitation LDH, (LD5), (ALT), Arginase 1 (liver type), Alpha-fetoprotein (AFP), Alkaline phosphatase, Alanine aminotransferase, Lactate dehydrogenase, and Bilirubin.
  • kidney markers include without limitation TNFa Receptor, Cystatin C, Lipocalin-type urinary prostaglandin D, synthatase (LPGDS), Hepatocyte growth factor receptor, Polycystin 2, Polycystin 1, Fibrocystin, Uromodulin, Alanine, aminopeptidase, N-acetyl-B-D-glucosaminidase, Albumin, and Retinol-binding protein (RBP).
  • Exemplary heart markers include without limitation Troponin I (TnI), Troponin T (TnT), CK, CKMB, Myoglobin, Fatty acid binding protein (FABP), CRP, D-dimer, S-100 protein, BNP, NT-proBNP, PAPP-A, Myeloperoxidase (MPO), Glycogen phosphorylase isoenzyme BB (GPBB), Thrombin Activatable Fibrinolysis Inhibitor (TAFI), Fibrinogen, Ischemia modified albumin (IMA), Cardiotrophin-1, and MLC-I (Myosin Light Chain-I).
  • TnI Troponin I
  • TnT Troponin T
  • CK Troponin T
  • CKMB Myoglobin
  • CRP D-dimer
  • S-100 protein S-100 protein
  • BNP BNP
  • NT-proBNP NT-proBNP
  • PAPP-A Myeloperoxidas
  • pancrease markers include without limitation Amylase, Pancreatitis-Assocoated protein (PAP-1), and Regeneratein proteins (REG).
  • PAP-1 Pancreatitis-Assocoated protein
  • REG Regeneratein proteins
  • Exemplary muscle tissue markers include without limitation Myostatin.
  • Exemplary blood markers include without limitation Erythopoeitin (EPO).
  • EPO Erythopoeitin
  • Exemplary bone markers include without limitation, Cross-linked N-telopeptides of bone type I collagen (NTx) Carboxyterminal cross-linking telopeptide of bone collagen, Lysyl-pyridinoline (deoxypyridinoline), Pyridinoline, Tartrate-resistant acid phosphatase, Procollagen type I C propeptide, Procollagen type I N propeptide, Osteocalcin (bone gla-protein), Alkaline phosphatase, Cathepsin K, COMP (Cartillage Oligimeric Matrix Protein), Osteocrin Osteoprotegerin (OPG), RANKL, sRANK, TRAP 5 (TRACP 5), Osteoblast Specific Factor 1 (OSF-1, Pleiotrophin), Soluble cell adhesion molecules, sTfR, sCD4, sCD8, sCD44, and Osteoblast Specific Factor 2 (OSF-2, Periostin).
  • NTx Cross-linked N-
  • markers according to the present invention are disease specific.
  • Exemplary cancer markers include without limitation PSA (total prostate specific antigen), Creatinine, Prostatic acid phosphatase, PSA complexes, Prostrate-specific gene-1, CA 12-5, Carcinoembryonic Antigen (CEA), Alpha feto protein (AFP), hCG (Human chorionic gonadotropin), Inhibin, CAA Ovarian C1824, CA 27.29, CA 15-3, CAA Breast C1924, Her-2, Pancreatic, CA 19-9, Carcinoembryonic Antigen, CAA pancreatic, Neuron-specific enolase, Angiostatin DcR3 (Soluble decoy receptor 3), Endostatin, Ep-CAM (MK-1), Free Immunoglobulin Light Chain Kappa, Free Immunoglobulin Light Chain Lambda, Herstatin, Chromogranin A, Adrenomedullin, Integrin, Epidermal growth factor receptor, Epidermal growth factor receptor-Ty
  • infectious disease conditions include without limitation: Viremia, Bacteremia, Sepsis, and markers: PMN Elastase, PMN elastase/ al-PI complex, Surfactant Protein D (SP-D), HBVc antigen, HBVs antigen, Anti-HBVc, Anti-HIV, T-supressor cell antigen, T-cell antigen ratio, T-helper cell antigen, Anti-HCV, Pyrogens, p24 antigen, Muramyl-dipeptide.
  • SP-D Surfactant Protein D
  • HBVc antigen HBVs antigen
  • Anti-HBVc Anti-HIV
  • T-supressor cell antigen T-cell antigen ratio
  • T-helper cell antigen Anti-HCV
  • Pyrogens Pyrogens
  • p24 antigen Muramyl-dipeptide.
  • Exemplary diabetes markers include without limitation C-Peptide, Hemoglobin Alc, Glycated albumin, Advanced glycosylation end products (AGEs), 1,5-anhydroglucitol, Gastric Inhibitory Polypeptide, Glucose, Hemoglobin, ANGPTL3 and 4.
  • Exemplary inflammation markers include without limitation Rheumatoid factor (RF), Antinuclear Antibody (ANA), C-reactive protein (CRP), Clara Cell Protein (Uteroglobin).
  • RF Rheumatoid factor
  • ANA Antinuclear Antibody
  • CRP C-reactive protein
  • Clara Cell Protein Uteroglobin
  • Exemplary allergy markers include without limitation Total IgE and Specific IgE.
  • autism markers include without limitation Ceruloplasmin, Metalothioneine, Zinc, Copper, B6, B12, Glutathione, Alkaline phosphatase, and Activation of apo-alkaline phosphatase.
  • Exemplary coagulation disorders markers include without limitation b-Thromboglobulin, Platelet factor 4, Von Willebrand factor.
  • a marker may be therapy specific.
  • COX inhibitors include without limitation TxB2 (Cox-1), 6-keto-PGF-1-alpha (Cox 2), 11-Dehydro-TxB-1a (Cox-1).
  • markers of the present include without limitation Leptin, Leptin receptor, and Procalcitonin, Brain S100 protein, Substance P, 8-Iso-PGF-2a.
  • Exemplary geriatric markers include without limitation, Neuron-specific enolase, GFAP, and S100B.
  • Exemplary markers of nutritional status include without limitation Prealbumin, Albumin, Retinol-binding protein (RBP), Transferrin, Acylation-Stimulating Protein (ASP), Adiponectin, Agouti-Related Protein (AgRP), Angiopoietin-like Protein 4 (ANGPTL4, FIAF), C-peptide, AFABP (Adipocyte Fatty Acid Binding Protein, FABP4) Acylation-Stimulating Protein (ASP), EFABP (Epidermal Fatty Acid Binding Protein, FABP5), Glicentin, Glucagon, Glucagon-Like Peptide-1, Glucagon-Like Peptide-2, Ghrelin, Insulin, Leptin, Leptin Receptor, PYY, RELMs, Resistin, amd sTfR (soluble Transferrin Receptor).
  • ASP Acylation-Stimulating Protein
  • AgRP Agouti-Related Protein
  • ANGPTL4
  • Exemplary markers of Lipid metabolism include without limitation Apo-lipoproteins (several), Apo-A1, Apo-B, Apo-C-CII, Apo-D, Apo-E.
  • Exemplary coagulation status markers include without limitation Factor I: Fibrinogen, Factor II: Prothrombin, Factor III: Tissue factor, Factor IV: Calcium, Factor V: Proaccelerin, Factor VI, Factor VII: Proconvertin, Factor VIII:, Anti-hemolytic factor, Factor IX: Christmas factor, Factor X: Stuart-Prower factor, Factor XI: Plasma thromboplastin antecedent, Factor XII: Hageman factor, Factor XIII: Fibrin-stabilizing factor, Prekallikrein, High-molecular-weight kininogen, Protein C, Protein S, D-dimer, Tissue plasminogen activator, Plasminogen, a2-Antiplasmin, Plasminogen activator inhibitor 1 (PAI1).
  • Exemplary monoclonal antibodies include those for EGFR, ErbB2, and IGF1R.
  • Exemplary tyrosine kinase inhibitors include without limitation Ab1, Kit, PDGFR, Src, ErbB2, ErbB 4, EGFR, EphB, VEGFR1-4, PDGFRb, FLt3, FGFR, PKC, Met, Tie2, RAF, and TrkA.
  • Exemplary Serine/Threoline Kinas Inhibitors include without limitation AKT, Aurora A/B/B, CDK, CDK (pan), CDK1-2, VEGFR2, PDGFRb, CDK4/6, MEK1-2, mTOR, and PKC-beta.
  • GPCR targets include without limitation Histamine Receptors, Serotonin Receptors, Angiotensin Receptors, Adrenoreceptors, Muscarinic Acetylcholine Receptors, GnRH Receptors, Dopamine Receptors, Prostaglandin Receptors, and ADP Receptors.
  • a therapeutic agent can include any substances that have therapeutic utility and/or potential.
  • substances include but are not limited to biological or chemical compounds such as simple or complex organic or inorganic molecules, peptides, proteins (e.g. antibodies) or a polynucleotides (e.g. anti-sense).
  • a vast array of compounds can be synthesized, for example polymers, such as polypeptides and polynucleotides, and synthetic organic compounds based on various core structures, and these can also be included as therapeutic agents.
  • various natural sources can provide compounds for screening, such as plant or animal extracts, and the like.
  • agent is used alone or in combination with another agent, having the same or different biological activity as the agents identified by the inventive screen.
  • the agents and methods also are intended to be combined with other therapies.
  • small molecule drugs are often measured by mass-spectrometry which can be imprecise.
  • ELISA (antibody-based) assays can be much more accurate and precise.
  • Physiological parameters include without limitation parameters such as temperature, heart rate/pulse, blood pressure, and respiratory rate.
  • Pharmacodynamic parameters include concentrations of biomarkers such as proteins, nucleic acids, cells, and cell markers. Biomarkers could be indicative of disease or could be a result of the action of a drug.
  • Pharmacokinetic (PK) parameters include without limitation drug and drug metabolite concentration. Identifying and quantifying the PK parameters in real time from a sample volume is extremely desirable for proper safety and efficacy of drugs. If the drug and metabolite concentrations are outside a desired range and/or unexpected metabolites are generated due to an unexpected reaction to the drug, immediate action may be necessary to ensure the safety of the patient. Similarly, if any of the pharmacodynamic (PD) parameters fall outside the desired range during a treatment regime, immediate action may have to be taken as well.
  • PD pharmacodynamic
  • a business method can comprise post prescription monitoring of drug therapy by monitoring trends in biomarkers over time.
  • the business method can comprise collecting at least one pharmacological parameter from an individual receiving a medication, said collecting step is effected by subjecting a sample of bodily fluid to reactants contained in a fluidic device, which is provided to said individual to yield a detectable signal indicative of said at least one pharmacological parameter; and cross referencing with the aid of a computer medical records of said individual with the at least one pharmacological parameter of said individual, thereby assisting said clinician in providing individualized medical treatment.
  • the devices, systems, and methods herein allow for automatic quantification of a pharmacological parameter of a patient as well as automatic comparison of the parameter with, for example, the patient's medical records which may include a history of the monitored parameter, or medical records of another group of subjects.
  • Coupling real-time analyte monitoring with an external device which can store data as well as perform any type of data processing or algorithm, for example provides a device that can assist with typical patient care which can include, for example, comparing current patient data with past patient data. Therefore, also described herein is a business method which effectively performs at least part of the monitoring of a patient that is currently performed by medical personnel.
  • a device, method, and system of the invention are used to perform an assay for human VEGFR2.
  • the example demonstrates a type of assay that can be performed at the point of care.
  • the capture surface of an assay unit can be coated onto the assay unit according to the assay, this example a VEGFR2 assay.
  • the inner surface of the assay unit (made from injection molded polystyrene similar to example in Figure 3A ) was exposed to a succession of coating reagents by aspiration and pneumatic ejection. Twenty microliters of each coating reagents were drawn into assay units and incubated at room temperature for 10 minutes.
  • the coating reagents used in this example are, as used in succession, Neutravidin (20ug/mL) in Carbonate-Bicarbonate buffer (pH 9), biotinylated "Capture antibody” (a monoclonal antibody directed to VEGFR2 at 20ug/mL) in Tris buffered saline, (pH 8), and a "fixative" reagent containing 3% bovine serum albumin in Tris-buffered saline. After the succession of coatings, the assay units were dried by exposure to dry air and stored desiccated.
  • Samples for analysis are then distributed to the assay unit diluted in a solution of 50 mM tris-buffer (pH 8) containing bovine serum albumin and isotonic sucrose for 20 minutes.
  • a reagent unit comprising a conjugate, a solution of Alkaline phosphatase (bovine intestine)-labeled monoclonal antibody directed to VEGFR2 (binding to a distinct epitope to the antibody of the capture surface) at 250 ng/mL in a stabilizer reagent from Biostab is provided to the assay unit for 10 minutes.
  • the assay unit was washed with a solution contained in a reagent unit (commercially available wash buffer from Assay Designs). The assay unit was washed 5 times. Then the assay unit was moved to collect and mix with another reagent contained in a different reagent, a solution of a commercially available luminogenic substrate for alkaline phosphatase (KPL Phosphaglo), and incubated for 10 minutes. The reaction of the assay in the assay unit was then detected by a detector assembly of the invention.
  • a reagent unit commercially available wash buffer from Assay Designs
  • Figure 12 demonstrates the VEGFR2 assay response using the method of the example.
  • the x axis scale is VEGFR2 concentration (pg/mL); the y scale is relative luminescence (counts). The curve was used to calibrate the modular assay unit and reagent units.
  • the lyophilized magnetizable bead pellet was re-suspended by adding 20 uL of whole blood then aspirating and dispensing at least 8 times (approximately 1.5 min) into a conical tube.
  • Blood was separated by placing the tip (in a vertical orientation) in a strong, horizontally oriented magnetic field. Typically 8 uL of essentially red cell free plasma with no observable hemolysis was recovered from a 20 ul blood sample (70% yield). Recovery of analytes (compared to plasma not exposed to the magnetic separation) was close to 100% for Protein-C, VEGF, PIGF, Insulin, GIP and GIP-1.
  • C-reactive protein is an acute-phase marker. Normal levels are in the high ng/mL to low ug/ml range. In any acute disease process, the human liver produces CRP and levels in blood can increase to hundreds of ug/ml. CRP has presented issues for prior art POC analytic systems because of the wide dynamic range of analyte to be measured (> 10 5 -fold).
  • a system as described herein comprising a fluid transfer device and a cartridge or device with arrays of assay and reagent units was developed.
  • Assay tips having monoclonal anti-CRP bound to their inner surface were mounted in cartridge together with a detector-antibody solution (alkaline-phosphatase labeled monoclonal anti-CRP (having a different epitope specificity than that on the tips), a wash solution and a chemiluminogenic alkaline phosphatase (PhosphaGLOTM) substrate from KPL.
  • a detector-antibody solution alkaline-phosphatase labeled monoclonal anti-CRP (having a different epitope specificity than that on the tips)
  • PhosphaGLOTM chemiluminogenic alkaline phosphatase
  • the cartridges were loaded with pre-diluted solutions of CRP used without further dilution.
  • the cartridges were processed by a system. Successively the CRP solution (10 uL), detector antibody (12 uL) were drawn into the tips incubated for 10 min at 34 °C then discarded. The tips were washed by four aspirations of 20 uL wash solution before 15 uL of substrate was aspirated into the tips. After 10 min at 37 °C, light emission was measured by the instrument for 5 s. CRP concentration was plotted against the assay signal (photon counts) and the data fitted to a 5-term polynomial function as shown below to generate a calibration function as shown in Figure 14 .
  • the modification assumes that the response of the assay is linearly proportional to the concentration of the detector antibody, as is the case in this example (data not shown).
  • Any carry-over of CRP in the diluted sample into the next reagent (detector antibody) will react rapidly with the reagent rendering it incapable of binding to antigen bound to the solid phase antibody.
  • the reduction in effective concentration is reduced in proportion to the CRP carried-over and can be accounted for with a factor (D - C*f)/D.
  • S Smax*(C/(C + C0.5))*(D - C*f)/D, wherein S is the assay signal, Smax is the maximum signal (corresponding to zero carry-over), C is the concentration of analyte, C0.5 is the concentration for half-maximal signal (no carry-over), D is the detector antibody concentration, and f is the fractional carryover.
  • Data can be then be viewed according to the dilution used to achieve the final concentration in each assay tip, and for each dilution level the responses fit to the same response showing that the dilutions are accurate and precise as shown in Figure 16 .
  • the model as described herein can be used to compute responses for any given dilution and set up algorithms to ensure that the analyte concentration in any tip within the calibration range.
  • Graphic means of representing the data are shown in Figure 17 , wherein the normalized assay response (B/Bmax) is plotted against the log normalized concentration (C/C0.5) for relative dilutions: 1:1 (solid line), 5:1 (dashed line), and 25:1 (dotted line).
  • Figures 18 and 19 illustrate a similar example as Figure 17 at different normalized concentrations.
  • Simple pattern recognition algorithms can be used to identify valid data for high concentration samples. For example, for most of the dose-response, the signal decreases with dilution.
  • concentrations derived by using the calibration function shown in Example 4 should correspond within some system imprecision with the known dilutions. If the calculated concentration for a low dilution is lower than would correspond with those for higher dilutions, the lower dilution result can be rejected.
  • dilution or serial dilution can provide a concentration precision as achieved by immunoassays at signal levels significantly greater (for example, > 10-fold) higher than the blank (zero analyte) signal but not close to the maximum signal (for example ⁇ 0.3*Max. signal). Serial dilution can allow the assay signal to be in this range.
  • an average value can be obtained.
  • An average value can also be achieved by making replicate measurements at a single dilution level.
  • a serial dilution approach as offered by the methods, systems, and device described herein can often eliminate errors due to non-linearity of dilution due to (for example) matrix effects from the sample.
  • Fluorescein is a well-known chemical and high affinity antibodies are known which are specific for the molecule. By attaching several fluorescein moieties to a protein such as albumin, an artificial analyte is created that can be measured by ELISA.
  • the example herein is set up on a microtiter plate to show the feasibility of such an assay and is easily translatable to a device or system of the invention as described herien.
  • Anti-fluorescein monoclonal antibody was attached to wells of 384-well microtiter plates to create a capture surface.
  • An assay is performed by adding a series of solutions to the wells and incubating at room temperature for 10 min at each stage when necessary.
  • 30 ul of known concentrations of a commercially available preparation of fluorescein-labeled bovine albumin (sample) with a ratio of about five fluoresceins per molecule were added to the wells.
  • 30 ul of alkaline phosphatase-labeled anti-fluorescein was added at a concentration of 100 ng/ml.
  • Fluorescein-labeled albumin (5 uL at various concentrations up to 80 ng/mL) dissolved in Tris-buffered saline containing bovine albumin at 3 mg/mL (buffer) was placed in polypropylene tubes and dried by exposure to low humidity air overnight. Complete drying was verified by weighing many tubes before and after drying and verifying the appropriate weight loss and a near-constant final weight was achieved. The analyte was recovered by adding 5 uL water, 20 uL human serum and 180 uL buffer and mixing. Control experiments were made by mixing 5 uL aliquots of analyte solution with 20 uL serum and 180 uL buffer.
  • Analyte recovery was measured using the assay as described herein. As shown below, the recovery of assay signal (and analyte) is essentially quantitative at all concentrations. It can be desirable to have good recovery (>90%), which is precise ( ⁇ 2% CV in recovery).
  • the assay dose-response is linear over the range of interest by having a low concentration of analyte and excess of the reagents. For example, a linear assay dose-response can be achieved by having sufficient capacity for antigen binding on the capture surface such that even at the highest level of analyte only a moderate proportion (for example, ⁇ 30%) of sites are occupied at the end of the binding reaction.
  • a linear assay dose-response can be achieved by having development of a signal less than the linear response of the detector (for example, a PMT with up to about 4 million photons per second). As described herein, systems and methods can fall within this range.
  • a linear assay dose-response can be achieved by development of a signal sufficiently high as to be precisely measured (for example, photon count rates greater than about 1,000 per second).
  • Assay tips were coated by aspiration of the following succession of reagents: 20 uL 5 ug/mL Rabbit anti-fluorescein (Molecular Probes # A6413) in carbonate buffer pH 9, 20 uL 3% bovine albumin in tris-buffered saline pH 8, and 20 uL 2.5 ug/mL bovine albumin labeled with fluorescein (Sigma-Aldrich A9771), each followed by incubation for 10 m and ejection of liquid. The tips were then washed three times by aspiration of bovine albumin in tris-buffered saline pH 8 followed by incubation 3% bovine albumin in tris-buffered saline pH 8.
  • Tips were then dried as described herein. These tips were used to assay samples containing goat anti-fluorescein by incubation of 20 uL aliquots of the following solutions in sequence: goat anti-fluorescein (sample) in tris-buffered saline pH 8 containing 3% BSA, alkaline phosphatase labeled Rabbit-anti-goat fluorescein at 100 ng/mL in Stabilzyme TM (a commercially available solvent), washing four times with Wash Buffer, and PhosphaGLO TM alkaline phosphatase chemiluminogenic substrate, each with an incubation at room temperature for 10 min.
  • Figure 21 shows a linear response similar to that in Figure 20 .
  • Table 2 Configurations of assays for candidate control analytes Capture surface reagent 1 Capture surface reagent 2 Analyte Detector: APase-labeled Anti-fluorescein Fluorescein-labeled albumin Anti-fluorescein Anti-fluorescein Fluorescein-labeled albumin Anti-fluotescein (species X) Anti X-Ig Avidin Biotinylated-species X-IgG Anti X-Ig Anti-biotin Biotin-labeled albumin Anti-biotin or Streptavidin Anti-digoxin Digoxin-labeled albumin Anti-digoxin Fluorescein-labeled albumin Anti-fluorescein (species X) Anti-X-Ig Anti-biotin Biotinylated anti-fluorescein Anti-fluorescein (species X) Anti-X-Ig Anti-biotin Biotinylated anti-fluorescein Anti-fluoresc
  • This example illustrates the predictability of response from an immunoassay for CRP using assay tips as described herein following initial addition of reagents, removal of the reaction product, washing the tips then reintroduction of some or all assay components.
  • the assay sequence was: tips were incubated in prototype instruments at 34C for 10 min in succession with (1) sample (CRP 0.3, 3, 30,150 and 300 ug/mL), diluted by the instrument 500 then 2000-fold (2) alkaline phosphatase labeled rabbit anti-goat IgG ["Dab”] (5 ng/mL) then washed three times and (3) with PhosphaGLO TM alkaline phosphatase chemiluminogenic substrate ["Substrate”].
  • the re-processed assay signals were linearly related (proportional) to the original assay signal.
  • the second substrate addition gave a higher signal relative to the original whereas reprocessed assays in which Dab and substrate were both introduced or those where sample, Dab and substrate were all reintroduced gave lower signals than the original.
  • all steps in an assay sequence can be examined for quality control to understand if they went as expected according to the expected relationship between the first and subsequent iterations of assay steps.
  • the assay result can either be rejected as incorrect or the later iterations of the assay result can be used as the appropriate assay response.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Immunology (AREA)
  • Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)
  • Hematology (AREA)
  • Biomedical Technology (AREA)
  • Physics & Mathematics (AREA)
  • Analytical Chemistry (AREA)
  • Pathology (AREA)
  • Urology & Nephrology (AREA)
  • Biochemistry (AREA)
  • General Physics & Mathematics (AREA)
  • Medicinal Chemistry (AREA)
  • Biotechnology (AREA)
  • Cell Biology (AREA)
  • Microbiology (AREA)
  • Food Science & Technology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Clinical Laboratory Science (AREA)
  • Organic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Medical Informatics (AREA)
  • Public Health (AREA)
  • Zoology (AREA)
  • Biophysics (AREA)
  • Wood Science & Technology (AREA)
  • Surgery (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Epidemiology (AREA)
  • Primary Health Care (AREA)
  • Sustainable Development (AREA)
  • Genetics & Genomics (AREA)
  • General Engineering & Computer Science (AREA)
  • Virology (AREA)

Claims (15)

  1. Cartouche destinée à la détection automatisée d'un analyte dans un échantillon de fluide corporel comprenant :
    un ensemble d'unités de dosage adressables configuré pour exécuter une réaction chimique qui génère un signal détectable indicatif de la présence ou de l'absence de l'analyte ; et
    un ensemble d'unités de réactifs adressables, dans laquelle une unité de réactif adressable individuelle de l'ensemble est adressée pour correspondre à une unité de dosage adressable individuelle de l'ensemble des unités de dosage, dans laquelle l'unité de réactif individuelle est configurée pour être calibrée en référence à l'unité de dosage individuelle correspondante avant que les ensembles ne soient assemblés sur la cartouche et dans laquelle l'unité de dosage individuelle de l'ensemble des unités de dosage adressables et l'unité de réactif individuelle de l'ensemble des unités de réactif adressables sont configurées pour être mobiles pour réaliser une communication fluidique, de telle sorte que les réactifs destinés à exécuter la réaction chimique soient amenés en contact avec la partie de l'échantillon dans l'unité de dosage.
  2. Cartouche selon la revendication 1, dans laquelle :
    (a) l'unité de réactif individuelle est configurée pour recevoir une unité de dosage mobile ;
    (b) l'unité de dosage individuelle comprend une pointe de dosage ;
    (c) l'unité de dosage individuelle est configurée pour exécuter un dosage immunologique ; ou
    (d) l'échantillon de fluide corporel est un échantillon de sang.
  3. Cartouche selon la revendication 1, comprenant en outre :
    (a) une unité de collecte d'échantillon configurée pour :
    (i) recevoir l'échantillon de fluide corporel ;
    (ii) recevoir un volume de l'échantillon de fluide corporel approximativement égal ou inférieur à 50 microlitres ; ou
    (iii) recevoir un volume de l'échantillon de fluide corporel qui est une seule goutte de sang ; ou
    (b) une unité de prétraitement configurée pour récupérer une partie de l'échantillon de fluide corporel pour exécuter la réaction chimique pour détecter l'analyte, et dans laquelle optionnellement l'échantillon de fluide corporel est un échantillon de sang complet et dans laquelle la partie est du plasma.
  4. Système pour la détection automatisée d'un analyte dans un échantillon de fluide corporel comprenant :
    (a) une cartouche selon la revendication 1 ; et
    (b) un assemblage de détection :
    (i) pour la détection du signal détectable indicatif de la présence ou de l'absence de l'analyte ;
    (ii) configuré pour détecter des intensités de signal amenées à être détectable à l'intérieur de la plage par une dilution de l'échantillon de fluide corporel ;
    (iii) configuré pour détecter des intensités de signal comprises entre environ 1000 et environ 1 million de comptes par seconde en utilisant un photomultiplicateur.
  5. Système selon la revendication 4, comprenant en outre :
    (a) un dispositif mécanique programmable configuré pour déplacer l'unité de dosage individuelle à partir d'un premier emplacement jusqu'à un second emplacement ;
    (b) un assemblage de communication destiné à transmettre un protocole basé sur l'analyte à détecter ;
    (c) un bloc de chauffage configuré pour recevoir l'unité de dosage individuelle ; ou
    (d) un bloc magnétique.
  6. Système selon la revendication 4, comprenant en outre un dispositif de transfert de fluide, dans lequel le dispositif de transfert de fluide :
    (a) est une pipette, et dans lequel optionnellement la pipette est une pipette à déplacement d'air ;
    (b) est automatisé ; ou
    (c) comprend une pluralité de têtes, dans lequel une tête individuelle de la pluralité de têtes est configurée pour venir en prise avec l'unité de dosage individuelle, et comprend un processeur programmable configuré pour diriger un transfert de fluide de l'échantillon de fluide corporel en provenance d'une unité de collecte d'échantillons, et le réactif en provenance de l'unité de réactif individuelle, dans l'unité de dosage individuelle ;
    et optionnellement :
    (i) dans lequel la configuration du processeur pour diriger le transfert de fluide réalise un degré de dilution de l'échantillon de fluide corporel dans l'ensemble d'unités de dosage pour obtenir des signaux indicatifs de la pluralité d'analytes détectés à l'intérieur d'une plage détectable, de telle sorte que ladite pluralité d'analytes soient détectables avec ledit système ; ou
    (ii) dans lequel le dispositif de transfert de fluide comprend en outre un moteur en communication avec le processeur programmable.
  7. Système selon la revendication 4, dans lequel :
    (a) l'échantillon de fluide corporel comprend au moins deux analytes qui sont présents à des concentrations qui diffèrent de 2 ordres de grandeur au moins ;
    (b) l'échantillon de fluide corporel comprend au moins deux analytes qui sont présents à des concentrations qui diffèrent de 5 ordres de grandeur au moins ;
    (c) un degré de dilution de l'échantillon de fluide corporel permet d'obtenir des signaux indicatifs de deux analytes au moins à l'intérieur de la plage détectable ;
    (d) l'échantillon de fluide corporel est inférieur à 50 µl environ ;
    (e) l'échantillon de fluide corporel est une seule goutte de sang ;
    (f) une tête individuelle d'un dispositif de transfert de fluide est configurée pour adhérer à l'unité de dosage individuelle ;
    (g) ladite unité de dosage individuelle fournit un site de réaction de dosage immunologique ; ou
    (h) ladite unité de dosage individuelle est une pointe pour pipette.
  8. Procédé de détection d'un analyte dans un échantillon de fluide corporel collecté chez un sujet comprenant :
    (a) la fourniture d'un échantillon de fluide corporel à la cartouche selon la revendication 1 ;
    (b) la possibilité dudit échantillon de réagir à l'intérieur d'au moins une unité de dosage ; et
    (c) la détection dudit signal détectable généré à partir dudit analyte collecté dans ledit échantillon de fluide corporel.
  9. Procédé selon la revendication 8, dans lequel l'échantillon de fluide corporel est du sang et le procédé comprend en outre la récupération du plasma contenu dans le sang.
  10. Système de détection automatisée d'un analyte dans une partie de plasma d'un échantillon de sang complet, comprenant :
    (a) une cartouche selon la revendication 1, dans lequel ladite cartouche est configurée en outre pour recevoir et pour traiter de manière automatique l'échantillon de sang complet pour obtenir la partie de plasma, à partir de laquelle un signal détectable indicatif de la présence ou de l'absence de l'analyte d'intérêt, est généré dans la cartouche ; et
    (b) un assemblage de détection pour détecter le signal détectable indicatif de la présence ou de l'absence de l'analyte.
  11. Procédé d'assemblage à la demande d'une cartouche selon la revendication 1, dans lequel la cartouche comprend un boîtier, ledit procédé comprenant :
    (i) le placement dans le boîtier, selon l'analyte à détecter, de l'ensemble des unités de dosage adressable, dans lequel l'unité de dosage individuelle de l'ensemble est configurée pour exécuter une réaction chimique qui détecte un analyte qui présente un intérêt commandée par ledit utilisateur final ;
    (ii) le placement dans le boîtier, selon l'analyte à détecter, de l'ensemble d'unités de réactifs ; et
    (iii) la fixation des ensembles (i) et (ii) à l'intérieur du boîtier de la cartouche.
  12. Procédé selon la revendication 11, comprenant en outre :
    (a) la sélection d'un analyte à détecter ;
    (b) le scellage de la cartouche ; ou
    (c) l'étiquetage de la cartouche avec une étiquette lisible qui indique l'analyte à détecter, et dans lequel optionnellement l'étiquette lisible est un code-barres ou un RFID.
  13. Procédé de détection automatisée d'une pluralité d'analytes dans un échantillon de fluide corporel collecté chez un sujet comprenant :
    (a) la fourniture de l'échantillon de fluide corporel à la cartouche selon la revendication 1 ;
    (b) la mise en prise de l'unité de dosage individuelle en utilisant un dispositif de transfert de fluide ;
    (c) le transfert de l'échantillon de fluide corporel à partir d'une unité de collecte d'échantillons jusqu'à l'unité de dosage individuelle en utilisant le dispositif de transfert de fluide ; et
    (d) le transfert d'un réactif à partir de l'unité de réactif individuelle jusqu'à l'unité de dosage d'analyse, en faisant réagir de ce fait le réactif avec l'échantillon de fluide corporel pour obtenir le signal indicatif de l'analyte individuel de la pluralité d'analytes détectés.
  14. Procédé selon la revendication 13, dans lequel :
    (a) le dispositif de transfert de fluide comprend une pluralité de têtes, dans lequel une tête individuelle de la pluralité de têtes est configurée pour se mettre en prise avec l'unité de dosage individuelle ; et dans lequel ledit dispositif de transfert de fluide comprend un processeur programmable configuré pour diriger le transfert de fluide de l'échantillon de fluide corporel à partir de l'unité de collecte d'échantillons et du réactif à partir de l'unité de réactif individuelle dans l'unité de dosage individuelle, comprenant en outre optionnellement l'apport d'instructions au processeur programmable, dans lequel optionnellement les instructions dirigent le transfert de l'échantillon de fluide corporel jusqu'à l'unité de dosage individuelle ;
    (b) l'étape de transfert de l'échantillon de fluide corporel réalise un degré de dilution de l'échantillon de fluide corporel dans l'unité de dosage individuelle pour fournir le signal indicatif de l'analyte individuel de la pluralité d'analytes détectés à l'intérieur d'une plage détectable ;
    (c) l'échantillon de fluide corporel comprend au moins deux analytes individuels qui sont présents à des concentrations qui diffèrent d'au moins 2 ordres de grandeur ;
    (d) l'échantillon de fluide corporel comprend au moins deux analytes individuels qui sont présents à des concentrations qui diffèrent d'au moins 5 ordres de grandeur ;
    (e) le degré de dilution de l'échantillon de fluide corporel permet d'obtenir des signaux indicatifs d'au moins deux analytes individuels à l'intérieur d'une plage détectable ;
    (f) le degré de dilution de l'échantillon de fluide corporel est détecté au moyen d'un photomultiplicateur et les au moins deux analytes individuels au moins se situent dans une plage comprise entre environ 1000 et environ 1 million de comptes par seconde ;
    (g) l'échantillon de fluide corporel est inférieur à 50 µl environ ;
    (h) l'échantillon de fluide corporel est une seule goutte de sang ; ou
    (i) le réactif dans l'unité de réactif individuelle est un substrat d'enzyme d'un dosage immunologique, comprenant en outre optionnellement la répétition de l'étape du transfert du réactif à partir de l'unité de réactif individuelle une fois que la réaction destinée à obtenir le signal indicatif de l'analyte individuel de la pluralité d'analytes détectés, a pris fin, en créant de ce fait une seconde réaction destinée à obtenir un second signal indicatif de l'analyte individuel, et dans lequel optionnellement une intensité du signal et une seconde intensité du second signal indicatif de l'analyte individuel, sont moyennées pour calculer l'intensité finale du signal indicatif de l'analyte individuel.
  15. Procédé destiné à mesurer un volume d'un échantillon de fluide biologique collecté chez un sujet, comprenant :
    (a) la réaction d'une quantité connue d'un analyte de contrôle dans ledit échantillon avec un réactif pour obtenir un signal détectable indicatif de la quantité d'analyte de contrôle, dans lequel ladite étape de réaction se produit dans une cartouche selon la revendication 1 ; et
    (b) la comparaison dudit signal détectable à un signal détectable escompté, dans lequel le signal escompté est indicatif d'un volume escompté de l'échantillon, et dans lequel ladite comparaison fournit une mesure dudit volume dudit échantillon mesuré ;
    comprenant optionnellement en outre :
    (a) la vérification du volume dudit échantillon lorsque la mesure du volume de l'échantillon est comprise à environ 50 % du volume escompté de l'échantillon ;
    (b)
    (i) la réaction dudit échantillon qui contient un analyte cible avec un réactif pour obtenir un signal détectable indicatif de l'analyte cible ; et
    (ii) la mesure de la quantité d'analyte cible dans l'échantillon sur la base dudit signal détectable indicatif de l'analyte cible et de la mesure dudit volume dudit échantillon de liquide ; ou
    (c)
    (i) le mélange de l'échantillon en présence de particules pouvant être aimantées dans une unité de collecte d'échantillons, dans lequel les particules pouvant être aimantées comprennent une surface de capture d'anticorps pour se lier à des parties non plasmiques de l'échantillon ;
    et
    (ii) l'application d'un champ magnétique, au-dessus de la zone de collection de plasma, à l'échantillon mélangé pour réaliser la suspension des parties non plasmiques de l'échantillon sur la zone de collecte de plasma, dans lequel optionnellement :
    (1) l'échantillon est un échantillon de sang ;
    (2) l'unité de collecte d'échantillon est un tube capillaire ;
    (3) l'échantillon est inférieur à 50 microlitres environ ;
    (4) le plasma récupéré est inférieur à 10 microlitres environ ;
    (5) l'échantillon n'est pas dilué ;
    (6) le mélange se produit en présence d'anticorps non liés à une surface solide ;
    (7) le mélange comprend le mélange suite à une action de seringue ; ou
    (8) le procédé est exécuté dans un système selon la revendication 4 ou la revendication 8 ; ou
    (d) la transmission du résultat de la comparaison à un utilisateur final, et dans lequel optionnellement le résultat est transmis de manière sans fil ;
    et dans lequel optionnellement :
    (a) l'analyte de contrôle n'est normalement pas présent dans ledit échantillon en une quantité détectable ;
    (b) un échantillon de liquide et l'échantillon de fluide corporel sont le même échantillon ;
    (c) l'analyte de contrôle ne réagit pas avec un analyte cible dans l'échantillon de fluide corporel ;
    (d) un échantillon de liquide et l'échantillon de fluide corporel sont des échantillons de liquide différents ;
    (e) l'analyte de contrôle est choisi parmi le groupe constitué par : l'albumine, la fluorescéine, l'IgG, la protéine C, l'albumine marquée à la fluorescéine, l'IgG marquée à la fluorescéine, l'anti-fluorescéine, l'anti-digoxigénine, l'albumine marquée à la digoxigénine, l'IgG marquée à la digoxigénine, des protéines combinées à la biotine, et l'IgG non humaine ;
    (f) la réaction est un dosage immunologique ;
    (g) la réaction est un ELISA ; ou
    (h) le procédé est exécuté dans un système selon la revendication 4 ou la revendication 8.
EP08836072.2A 2007-10-02 2008-10-02 Dispositifs modulaires à utiliser sur place et leurs utilisations Active EP2205968B1 (fr)

Priority Applications (5)

Application Number Priority Date Filing Date Title
DK13178059.5T DK2657699T3 (en) 2007-10-02 2008-10-02 Modular point-of-care devices and their applications
EP20187805.5A EP3756767B1 (fr) 2007-10-02 2008-10-02 Dispositifs modulaires a utiliser sur place et leurs utilisations
EP24172878.1A EP4450163A3 (fr) 2007-10-02 2008-10-02 Dispositifs modulaires de point d'intervention et leurs utilisations
EP13178059.5A EP2657699B1 (fr) 2007-10-02 2008-10-02 Dispositifs modulaires à utiliser sur place et leurs utilisations
EP17155280.5A EP3181228B1 (fr) 2007-10-02 2008-10-02 Dispositifs modulaires à utiliser sur place et leurs utilisations

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US99746007P 2007-10-02 2007-10-02
PCT/US2008/078636 WO2009046227A1 (fr) 2007-10-02 2008-10-02 Dispositifs modulaires à utiliser sur place et leurs utilisations

Related Child Applications (4)

Application Number Title Priority Date Filing Date
EP24172878.1A Division EP4450163A3 (fr) 2007-10-02 2008-10-02 Dispositifs modulaires de point d'intervention et leurs utilisations
EP13178059.5A Division EP2657699B1 (fr) 2007-10-02 2008-10-02 Dispositifs modulaires à utiliser sur place et leurs utilisations
EP17155280.5A Division EP3181228B1 (fr) 2007-10-02 2008-10-02 Dispositifs modulaires à utiliser sur place et leurs utilisations
EP20187805.5A Division EP3756767B1 (fr) 2007-10-02 2008-10-02 Dispositifs modulaires a utiliser sur place et leurs utilisations

Publications (3)

Publication Number Publication Date
EP2205968A1 EP2205968A1 (fr) 2010-07-14
EP2205968A4 EP2205968A4 (fr) 2010-09-29
EP2205968B1 true EP2205968B1 (fr) 2013-11-20

Family

ID=40509067

Family Applications (5)

Application Number Title Priority Date Filing Date
EP08836072.2A Active EP2205968B1 (fr) 2007-10-02 2008-10-02 Dispositifs modulaires à utiliser sur place et leurs utilisations
EP20187805.5A Active EP3756767B1 (fr) 2007-10-02 2008-10-02 Dispositifs modulaires a utiliser sur place et leurs utilisations
EP24172878.1A Pending EP4450163A3 (fr) 2007-10-02 2008-10-02 Dispositifs modulaires de point d'intervention et leurs utilisations
EP17155280.5A Active EP3181228B1 (fr) 2007-10-02 2008-10-02 Dispositifs modulaires à utiliser sur place et leurs utilisations
EP13178059.5A Active EP2657699B1 (fr) 2007-10-02 2008-10-02 Dispositifs modulaires à utiliser sur place et leurs utilisations

Family Applications After (4)

Application Number Title Priority Date Filing Date
EP20187805.5A Active EP3756767B1 (fr) 2007-10-02 2008-10-02 Dispositifs modulaires a utiliser sur place et leurs utilisations
EP24172878.1A Pending EP4450163A3 (fr) 2007-10-02 2008-10-02 Dispositifs modulaires de point d'intervention et leurs utilisations
EP17155280.5A Active EP3181228B1 (fr) 2007-10-02 2008-10-02 Dispositifs modulaires à utiliser sur place et leurs utilisations
EP13178059.5A Active EP2657699B1 (fr) 2007-10-02 2008-10-02 Dispositifs modulaires à utiliser sur place et leurs utilisations

Country Status (17)

Country Link
US (22) US8088593B2 (fr)
EP (5) EP2205968B1 (fr)
JP (9) JP5511669B2 (fr)
KR (5) KR101844172B1 (fr)
CN (6) CN104297507B (fr)
AU (2) AU2008308686B2 (fr)
BR (2) BRPI0820328B8 (fr)
CA (5) CA2934220C (fr)
DK (2) DK2657699T3 (fr)
ES (2) ES2818194T3 (fr)
HK (4) HK1206422A1 (fr)
IL (8) IL204877A (fr)
MX (2) MX352987B (fr)
NZ (1) NZ584963A (fr)
RU (2) RU2540424C2 (fr)
SG (3) SG188082A1 (fr)
WO (1) WO2009046227A1 (fr)

Families Citing this family (243)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR101381331B1 (ko) 2005-05-09 2014-04-04 테라노스, 인코포레이티드 현장진료 유체 시스템 및 그 용도
EP2205968B1 (fr) * 2007-10-02 2013-11-20 Theranos, Inc. Dispositifs modulaires à utiliser sur place et leurs utilisations
JP5749156B2 (ja) * 2008-04-05 2015-07-15 シングル セル テクノロジー, インコーポレイテッドSingle Cell Technology, Inc. 生理活性物質の生産のための単一細胞を選抜する方法
US20100056766A1 (en) * 2008-08-27 2010-03-04 Abbott Laboratories Purification of biological conjugates by size exclusion chromatography
EP2389247B1 (fr) 2009-01-23 2017-03-01 Biotix, Inc. Plateaux d'embout de pipette antistatiques
US8790916B2 (en) 2009-05-14 2014-07-29 Genestream, Inc. Microfluidic method and system for isolating particles from biological fluid
CA3081708C (fr) 2009-10-19 2023-10-03 Theranos Ip Company, Llc Systeme de capture et d'analyse integre de donnees de sante
JP5570240B2 (ja) * 2010-02-22 2014-08-13 アークレイ株式会社 試料の分析処理におけるデータ出力方法、分析装置、分析システム、前記方法を実施するためのプログラム、およびこのプログラムの記憶媒体
WO2011123649A1 (fr) * 2010-03-31 2011-10-06 Abbott Point Of Care, Inc. Procédé et appareil pour mélanger sélectivement des réactifs dans une analyse d'échantillon de fluide biologique sensiblement non dilué
DE102010022017A1 (de) 2010-05-29 2011-12-01 Gerstel Systemtechnik Gmbh & Co.Kg Verfahren zur Probenvorbereitung bei chromatographischen Trennmethoden und Vorrichtungen zur Durchführung einer Probenvorbereitung
US9180448B2 (en) * 2010-07-06 2015-11-10 Becton, Dickinson And Company Method and apparatus for identification of bacteria
DE102010031240A1 (de) * 2010-07-12 2012-01-12 Hamilton Bonaduz Ag Pipettierspitze mit hydrophober Oberflächenausbildung
CN102375055A (zh) * 2010-08-19 2012-03-14 中国人民解放军军事医学科学院微生物流行病研究所 一种多重检测免疫层析芯片
US9433939B2 (en) 2010-08-27 2016-09-06 Hewlett-Packard Development Company, L.P. Liquid dispensing assembly frame
US9645162B2 (en) * 2010-08-27 2017-05-09 Hewlett-Packard Development Company, L.P. Automated assay fluid dispensing
JP5694726B2 (ja) 2010-09-30 2015-04-01 富士フイルム株式会社 検査方法および装置
US8951781B2 (en) 2011-01-10 2015-02-10 Illumina, Inc. Systems, methods, and apparatuses to image a sample for biological or chemical analysis
AU2013205019B2 (en) * 2011-01-21 2015-12-10 Labrador Diagnostics Llc Systems and methods for sample use maximization
EP4024029A3 (fr) * 2011-01-21 2022-09-14 Labrador Diagnostics LLC Systèmes et procédés de maximisation d'utilisation d'échantillon
US20140127713A1 (en) * 2011-06-28 2014-05-08 Femke Karina de Theije Means for the examination of body fluids
FI20115785A0 (fi) 2011-08-08 2011-08-08 Thermo Fisher Scientific Oy Menetelmä ja laite automaattiseen analyysiin
WO2013021101A1 (fr) 2011-08-08 2013-02-14 Thermo Fisher Scientific Oy Procédé et appareil d'analyse automatisée
US9664702B2 (en) 2011-09-25 2017-05-30 Theranos, Inc. Fluid handling apparatus and configurations
US8380541B1 (en) 2011-09-25 2013-02-19 Theranos, Inc. Systems and methods for collecting and transmitting assay results
US9268915B2 (en) 2011-09-25 2016-02-23 Theranos, Inc. Systems and methods for diagnosis or treatment
US9632102B2 (en) 2011-09-25 2017-04-25 Theranos, Inc. Systems and methods for multi-purpose analysis
US9619627B2 (en) 2011-09-25 2017-04-11 Theranos, Inc. Systems and methods for collecting and transmitting assay results
US20140170735A1 (en) 2011-09-25 2014-06-19 Elizabeth A. Holmes Systems and methods for multi-analysis
US8840838B2 (en) 2011-09-25 2014-09-23 Theranos, Inc. Centrifuge configurations
US8435738B2 (en) * 2011-09-25 2013-05-07 Theranos, Inc. Systems and methods for multi-analysis
US8475739B2 (en) 2011-09-25 2013-07-02 Theranos, Inc. Systems and methods for fluid handling
US10012664B2 (en) 2011-09-25 2018-07-03 Theranos Ip Company, Llc Systems and methods for fluid and component handling
US9250229B2 (en) 2011-09-25 2016-02-02 Theranos, Inc. Systems and methods for multi-analysis
US20140308661A1 (en) * 2011-09-25 2014-10-16 Theranos, Inc. Systems and methods for multi-analysis
US9810704B2 (en) 2013-02-18 2017-11-07 Theranos, Inc. Systems and methods for multi-analysis
CN103946364B (zh) 2011-09-25 2018-04-24 赛拉诺斯知识产权有限责任公司 用于多重分析的系统和方法
WO2013049782A2 (fr) * 2011-09-30 2013-04-04 Pandora Genomics, LLC Système, appareil et procédé d'évaluation d'échantillons ou d'analytes à l'aide d'un dispositif de site de soins
JP2014533824A (ja) * 2011-11-16 2014-12-15 ライカ・バイオシステムズ・メルボルン・プロプライエタリー・リミテッドＬｅｉｃａ Ｂｉｏｓｙｓｔｅｍｓ Ｍｅｌｂｏｕｒｎｅ Ｐｔｙ Ｌｔｄ 生体サンプル処理装置
US9557287B2 (en) 2012-01-24 2017-01-31 Koninklijke Philips N.V. Cartridge for processing a fluid
WO2013184625A2 (fr) * 2012-06-05 2013-12-12 Siemens Healthcare Diagnostics Inc. Détermination de qualité d'échantillon de sérum
US10408786B2 (en) 2012-06-14 2019-09-10 ChemiSensor, LLP Distributable chemical sampling and sensing system
US20130337477A1 (en) * 2012-06-14 2013-12-19 ChemiSensor LLP Distributable Chemical Sampling and Sensing System Process
US9500639B2 (en) 2012-07-18 2016-11-22 Theranos, Inc. Low-volume coagulation assay
MX381057B (es) 2012-07-18 2025-03-12 Labrador Diagnostics Llc Centrífuga compacta de alta velocidad para utilizarse con pequeños volúmenes de muestra.
AU2013295679A1 (en) 2012-07-25 2015-01-29 Theranos, Inc. Image analysis and measurement of biological samples
CN111067547A (zh) 2012-09-06 2020-04-28 赛拉诺斯知识产权有限责任公司 用于体液样品收集的系统、装置和方法
US9636062B2 (en) 2012-09-06 2017-05-02 Theranos, Inc. Systems, devices, and methods for bodily fluid sample collection
US9427184B2 (en) 2012-09-06 2016-08-30 Theranos, Inc. Systems, devices, and methods for bodily fluid sample collection
AU2013315800A1 (en) 2012-09-11 2015-03-12 Theranos Ip Company, Llc Information management systems and methods using a biological signature
US20140114676A1 (en) 2012-10-23 2014-04-24 Theranos, Inc. Drug Monitoring and Regulation Systems and Methods
US20150293085A1 (en) * 2012-10-31 2015-10-15 Astute Medical, Inc. Quantitative lateral flow assay
CN103808916B (zh) * 2012-11-13 2017-06-16 中国科学院深圳先进技术研究院 体液检测装置
US9386948B2 (en) 2012-12-05 2016-07-12 Theranos, Inc. Systems, devices, and methods for bodily fluid sample transport
EP3666188A1 (fr) 2012-12-05 2020-06-17 Theranos IP Company, LLC Systèmes, dispositifs et procédés de collecte et de transport d'échantillons de fluides corporels
US10248765B1 (en) 2012-12-05 2019-04-02 Theranos Ip Company, Llc Systems, devices, and methods for bodily fluid sample collection, transport, and handling
CA2891513A1 (fr) 2012-12-05 2014-06-12 Theranos, Inc. Systemes, dispositifs et procedes de collecte et de transport d'echantillons de liquides organiques
US20140358036A1 (en) * 2012-12-05 2014-12-04 Theranos, Inc. Bodily Fluid Sample Collection and Transport
US9051599B2 (en) 2012-12-10 2015-06-09 Theranos, Inc. Rapid, low-sample-volume cholesterol and triglyceride assays
WO2014093397A1 (fr) * 2012-12-12 2014-06-19 Green Domain Design, Llc Appareil d'analyse
US11320418B2 (en) 2012-12-12 2022-05-03 Iassay, Inc. Modular hand-held point of care testing system
EP2743694A1 (fr) * 2012-12-14 2014-06-18 Numares GmbH Procédé d'enrichissement d'un échantillon avec des informations spécifiques et système de tube d'échantillon
US9599610B2 (en) * 2012-12-19 2017-03-21 Dnae Group Holdings Limited Target capture system
US9995742B2 (en) * 2012-12-19 2018-06-12 Dnae Group Holdings Limited Sample entry
US9805407B2 (en) * 2013-01-25 2017-10-31 Illumina, Inc. Methods and systems for using a cloud computing environment to configure and sell a biological sample preparation cartridge and share related data
CN109813923A (zh) * 2013-02-18 2019-05-28 赛拉诺斯知识产权有限责任公司 用于采集和传输测定结果的系统和方法
US10401373B1 (en) 2013-02-18 2019-09-03 Theranos Ip Company, Llc Systems and methods for analyte testing and laboratory oversight
KR20150119334A (ko) 2013-02-18 2015-10-23 테라노스, 인코포레이티드 생체시료의 이미지 분석 및 측정
US11008628B1 (en) 2013-02-18 2021-05-18 Labrador Diagnostics Llc Systems and methods for analyte testing and laboratory oversight
CA2898477A1 (fr) * 2013-02-18 2014-08-21 Theranos, Inc. Systemes et procedes d'analyse multiple
CA2902484C (fr) 2013-02-26 2021-05-18 Astute Medical, Inc. Evaluation d'ecoulement lateral avec retenteur de bande d'essai
EP3595246A1 (fr) 2013-03-04 2020-01-15 Theranos IP Company, LLC Procédés et systèmes de connectivité de réseau
EP3540444B1 (fr) 2013-03-11 2022-10-26 Cue Health Inc. Systèmes et procédés de détection et de quantification d'analytes
US10545161B2 (en) 2013-03-11 2020-01-28 Cue Health Inc. Systems and methods for detection and quantification of analytes
US20140252079A1 (en) * 2013-03-11 2014-09-11 Promega Corporation Analyzer with machine readable protocol prompting
US9623409B2 (en) 2013-03-11 2017-04-18 Cue Inc. Cartridges, kits, and methods for enhanced mixing for detection and quantification of analytes
AU2013202778A1 (en) * 2013-03-14 2014-10-02 Gen-Probe Incorporated Systems, methods, and apparatuses for performing automated reagent-based assays
EP2972331B1 (fr) 2013-03-15 2018-10-17 Siemens Healthcare Diagnostics Inc. Dispositif de distribution microfluidique
SG11201507272RA (en) 2013-03-15 2015-10-29 Theranos Inc Nuclei acid amplification
CN105229465A (zh) 2013-03-15 2016-01-06 赛拉诺斯股份有限公司 用于样品制备的装置、系统和方法
US9359632B2 (en) 2013-03-15 2016-06-07 Theranos, Inc. Devices, systems and methods for sample preparation
WO2014145291A1 (fr) 2013-03-15 2014-09-18 Theranos, Inc. Amplification d'acide nucléique
US9416776B2 (en) * 2013-03-15 2016-08-16 Siemens Healthcare Diagnostics Inc. Microfluidic distributing device
MX365324B (es) 2013-03-15 2019-05-29 Theranos Ip Co Llc Metodos y dispositivos para recoleccion de muestras y separacion de muestras.
PL2970922T3 (pl) 2013-03-15 2018-06-29 Theranos, Inc. Termostabilna ligaza łącząca tępe końce i sposoby jej wykorzystania
CN115096658A (zh) 2013-03-15 2022-09-23 赛拉诺斯知识产权有限责任公司 用于体液样品收集的系统、装置和方法
CN108445242B (zh) 2013-03-15 2022-03-04 Hycor生物医学有限责任公司 进行样本的冷光和荧光测量的装置和相关方法
ES2729637T3 (es) 2013-03-15 2019-11-05 Theranos Ip Co Llc Amplificación de ácidos nucleicos
AU2014241182A1 (en) * 2013-03-27 2015-09-24 Theranos Ip Company, Llc Biological sample processing
ES2756098T3 (es) 2013-03-27 2020-04-27 Theranos Ip Co Llc Métodos, dispositivos y sistemas para el análisis de muestras
EP3570040B1 (fr) 2013-04-05 2024-02-14 F. Hoffmann-La Roche AG Procédé d'analyse d'un échantillon biologique
US10222375B2 (en) 2013-07-17 2019-03-05 Gold Standard Diagnostics Process and machine for automated agglutination assays with image automated evaluation
US20150309025A1 (en) * 2013-07-17 2015-10-29 Gold Standard Diagnostics Process and machine for automated agglutination assays
US10422806B1 (en) 2013-07-25 2019-09-24 Theranos Ip Company, Llc Methods for improving assays of biological samples
CN105555336B (zh) 2013-08-05 2019-04-30 康迈德医疗器械有限公司 顺应性的贴片泵
EP3042208A4 (fr) 2013-09-06 2017-04-19 Theranos, Inc. Systèmes et procédés pour détection de maladies infectieuses
MX2016002797A (es) 2013-09-06 2016-05-26 Theranos Inc Dispositivos, sistemas, metodos y equipos para recibir un hisopo.
US10943689B1 (en) 2013-09-06 2021-03-09 Labrador Diagnostics Llc Systems and methods for laboratory testing and result management
US11545241B1 (en) 2013-09-07 2023-01-03 Labrador Diagnostics Llc Systems and methods for analyte testing and data management
MX2016002851A (es) * 2013-09-08 2016-06-17 Theranos Inc Metodos y sistemas para obtener muestras clinicas.
US20180020823A1 (en) * 2013-09-08 2018-01-25 Theranos, Inc. Methods and systems for obtaining clinical samples
JP6700173B2 (ja) * 2013-09-24 2020-05-27 ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア ターゲット検出方法及びシステム
EP3061062B1 (fr) 2013-10-24 2022-11-16 Labrador Diagnostics LLC Systèmes et procédés de commande de tests de laboratoire et de fourniture des résultats de ceux-ci
US20150164398A1 (en) 2013-11-11 2015-06-18 Theranos, Inc. Methods and systems for a sample collection device with a novelty exterior
ES2716909T3 (es) * 2013-11-12 2019-06-17 Boditechmed Inc Cubeta de múltiples pocillos dotada de medios integrados de reacción y de detección
US11360107B1 (en) 2014-02-25 2022-06-14 Labrador Diagnostics Llc Systems and methods for sample handling
EP3114451B1 (fr) 2014-03-05 2022-10-19 Labrador Diagnostics LLC Dispositif pour séparation d'échantillons
JP2017507730A (ja) 2014-03-12 2017-03-23 セラノス， インコーポレイテッドＴｈｅｒａｎｏｓ， Ｉｎｃ． 体液サンプル収集のためのシステム、機器、及び方法
US10139348B2 (en) 2014-03-20 2018-11-27 Universal Bio Research Co., Ltd. Lightguide aggregate inspection device and inspection method of the same
USD745423S1 (en) 2014-05-12 2015-12-15 Cue Inc. Automated analyzer test cartridge and sample collection device for analyte detection
MX2016016234A (es) * 2014-06-11 2017-10-02 Theranos Inc Metodos, dispositivos y sistemas para analisis de muestras.
AU2015280423A1 (en) * 2014-06-23 2017-02-02 The Charles Stark Draper Laboratory, Inc. Injection well identification using tracer particles
WO2016007886A1 (fr) 2014-07-11 2016-01-14 Northwestern University Biocapteur à base de levure
EP3177933B1 (fr) * 2014-08-06 2020-02-19 Société des Produits Nestlé S.A. Biomarqueurs pour prédire le degré de perte de poids
WO2016037051A1 (fr) 2014-09-04 2016-03-10 Theranos, Inc. Pathogène et test de résistance antimicrobienne
EP2995937A1 (fr) * 2014-09-15 2016-03-16 Sensirion AG Puce de capteur chimique intégré
WO2016044673A1 (fr) 2014-09-17 2016-03-24 Theranos, Inc. Amplification d'acide nucléique multi-étapes hybride
US9506908B2 (en) 2014-10-06 2016-11-29 Alveo Technologies, Inc. System for detection of analytes
US10352899B2 (en) 2014-10-06 2019-07-16 ALVEO Technologies Inc. System and method for detection of silver
US10196678B2 (en) 2014-10-06 2019-02-05 ALVEO Technologies Inc. System and method for detection of nucleic acids
US10627358B2 (en) 2014-10-06 2020-04-21 Alveo Technologies, Inc. Method for detection of analytes
US9921182B2 (en) 2014-10-06 2018-03-20 ALVEO Technologies Inc. System and method for detection of mercury
WO2016057749A1 (fr) 2014-10-08 2016-04-14 Theranos, Inc. Procédés et dispositifs de test de diagnostic en temps réel (rdt) pour ebola et d'autres maladies infectieuses
US10137453B2 (en) 2014-12-10 2018-11-27 Biotix, Inc. Static-defeating apparatus for pipette tips
US10730053B2 (en) 2014-12-10 2020-08-04 Biotix, Inc. Static-defeating apparatus for pipette tips
USD865216S1 (en) * 2014-12-10 2019-10-29 Biotix, Inc. Pipette tip sheet
USD815753S1 (en) 2014-12-10 2018-04-17 Biotix, Inc. Pipette tip sheet
USD849962S1 (en) * 2014-12-10 2019-05-28 Biotix, Inc. Pipette tip retention sheet
US20160238627A1 (en) 2015-02-13 2016-08-18 Abbott Laboratories Decapping and capping apparatus, systems and methods for use in diagnostic analyzers
US10677811B2 (en) 2015-02-27 2020-06-09 Mastaplex Ltd. Sample receptacle, sample container and method of use
CA3017108A1 (fr) * 2015-03-12 2016-09-15 The Trustees Of The University Of Pennsylvania Systeme, procede et dispositif de culture automatisee a haut debit d'organismes genetiquement modifies
JP2016191668A (ja) * 2015-03-31 2016-11-10 ソニー株式会社 電気的特性測定方法、電気的特性測定装置、及び血液状態解析システム
CN107743518A (zh) * 2015-04-08 2018-02-27 贝克顿·迪金森公司 用于从半固体表面收集微生物生长的设备和装置
EP3288459B1 (fr) * 2015-04-29 2023-09-20 Revvity Health Sciences, Inc. Appareil de prélèvement et de distribution de spécimens
EP3093656A1 (fr) * 2015-05-13 2016-11-16 ARKRAY, Inc. Outil et système analytiques
CN104865395A (zh) * 2015-05-21 2015-08-26 上海儒克生物科技有限公司 生物应用机器人、机器人执行模块及执行方法
CN107771285A (zh) 2015-06-08 2018-03-06 阿奎尔诊断有限公司 方法
EP4060344A1 (fr) 2015-06-08 2022-09-21 Arquer Diagnostics Limited Procédés et kits
US10775370B2 (en) * 2015-07-17 2020-09-15 Stat-Diagnostica & Innovation, S.L. Fluidic system for performing assays
CA2992596C (fr) 2015-07-17 2023-08-22 Cue Inc. Systemes et procedes pour la detection amelioree et la quantification de substances a analyser
US10371606B2 (en) 2015-07-21 2019-08-06 Theraos IP Company, LLC Bodily fluid sample collection and transport
JP2018528411A (ja) 2015-07-21 2018-09-27 セラノス， インコーポレイテッドＴｈｅｒａｎｏｓ， Ｉｎｃ． 体液サンプル収集、輸送および取扱いのためのシステム、機器、ならびに方法
CN113358860A (zh) * 2015-07-23 2021-09-07 中尺度技术有限责任公司 自动化分析系统及在该系统中实施分析的方法
US11458205B2 (en) 2015-08-04 2022-10-04 Duke University Genetically encoded intrinsically disordered stealth polymers for delivery and methods of using same
WO2017044888A1 (fr) 2015-09-09 2017-03-16 Theranos, Inc. Procédés et dispositifs de collecte et de séparation d'échantillons
JP6952683B2 (ja) 2015-09-17 2021-10-20 エス．ディー．サイト ダイアグノスティクス リミテッド 身体試料中の実体を検出する方法および装置
EP3359115A4 (fr) 2015-10-09 2019-03-20 Theranos, Inc. Collecte et transport d'un échantillon de liquide corporel
US11752213B2 (en) 2015-12-21 2023-09-12 Duke University Surfaces having reduced non-specific binding and antigenicity
EP3397972A2 (fr) * 2015-12-31 2018-11-07 Universal Diagnostics, S.L. Systèmes et procédés automatiques, outil de préparation d'échantillon personnalisable, script logiciel, et programme d'étalonnage pour détection de métabolites et lipides
WO2017168411A1 (fr) 2016-03-30 2017-10-05 S.D. Sight Diagnostics Ltd Dispositif de traitement d'images destiné à l'identification de parasites du sang
JP2017185192A (ja) * 2016-03-31 2017-10-12 カシオ計算機株式会社 電子機器、報知方法及びプログラム
CN109073658B (zh) 2016-04-14 2021-07-09 豪夫迈·罗氏有限公司 用于测定体液样品中的靶分析物的浓度的方法
CN105865873A (zh) * 2016-05-05 2016-08-17 柳州市妇幼保健院 滤纸干血斑血红蛋白制备盒
US11307196B2 (en) 2016-05-11 2022-04-19 S.D. Sight Diagnostics Ltd. Sample carrier for optical measurements
CN109564209B (zh) 2016-05-11 2022-05-31 思迪赛特诊断有限公司 对样品实施的光学测量
WO2017210476A1 (fr) 2016-06-01 2017-12-07 Duke University Biocapteurs ne s'encrassant pas
CN109313190A (zh) * 2016-06-17 2019-02-05 西门子医疗保健诊断公司 通过流体样品再利用而使流体样品多重化的设备、方法和试剂盒
US10989724B1 (en) 2016-07-29 2021-04-27 Labrador Diagnostics Llc Systems and methods for multi-analysis
US20180032954A1 (en) * 2016-07-29 2018-02-01 Abbott Laboratories System and method for inventory sharing in a laboratory management system
US11112418B1 (en) * 2016-07-29 2021-09-07 Labrador Diagnostics Llc Systems and methods for multi-analysis
US11465141B2 (en) 2016-09-23 2022-10-11 Alveo Technologies, Inc. Methods and compositions for detecting analytes
JP2020500150A (ja) 2016-09-23 2020-01-09 デューク ユニバーシティ 下限臨界溶液温度挙動を有する非反復かつ非構造的ポリペプチド
TWI638178B (zh) * 2016-10-05 2018-10-11 旺矽科技股份有限公司 電測裝置、電測方法及針座電路結構
US20180135456A1 (en) * 2016-11-17 2018-05-17 General Electric Company Modeling to detect gas turbine anomalies
CN115192090A (zh) * 2016-11-23 2022-10-18 巴德股份有限公司 单插入多试样的活检装置
LU93333B1 (en) * 2016-12-06 2018-06-08 Stratec Biomedical Ag Transfer Tool for use in automated analyser systems
BE1024369B1 (nl) * 2016-12-12 2018-01-31 Anne Vanaken Apparaat voor oogonderzoek
US11648200B2 (en) 2017-01-12 2023-05-16 Duke University Genetically encoded lipid-polypeptide hybrid biomaterials that exhibit temperature triggered hierarchical self-assembly
WO2018140540A1 (fr) 2017-01-25 2018-08-02 Cue Health Inc. Systèmes et procédés pour la détection améliorée et la quantification de substances à analyser
EP3579975A4 (fr) * 2017-02-13 2021-03-24 Bio-rad Laboratories, Inc. Système, procédé et dispositif de formation d'une série d'émulsions
US11181481B2 (en) 2017-03-08 2021-11-23 Optofluidic Bioassay, Llc Optofluidic diagnostics system
US11857966B1 (en) 2017-03-15 2024-01-02 Labrador Diagnostics Llc Methods and devices for sample collection and sample separation
JP2020513108A (ja) * 2017-04-07 2020-04-30 イージーディエックス インコーポレイテッドＥａｓｙＤｘ，Ｉｎｃ． 臨床現場即時検査（ｐｏｃｔ）カートリッジ
US11554097B2 (en) 2017-05-15 2023-01-17 Duke University Recombinant production of hybrid lipid-biopolymer materials that self-assemble and encapsulate agents
US11680083B2 (en) 2017-06-30 2023-06-20 Duke University Order and disorder as a design principle for stimuli-responsive biopolymer networks
US10660619B2 (en) 2017-07-19 2020-05-26 Evanostics Llc Cartridges for oral fluid analysis and methods of use
KR20190016011A (ko) * 2017-08-07 2019-02-15 울산과학기술원 자성 입자를 이용한 유체 분리 시스템 및 방법
EP3444033B1 (fr) * 2017-08-18 2020-01-08 CTC Analytics AG Cartouche pour des dosages chimiques ou biologiques
CN107356587B (zh) * 2017-08-24 2024-03-01 北京贝泰科技有限公司 一种光激化学发光即时检测系统
EP3673268A1 (fr) * 2017-08-26 2020-07-01 AJ Innuscreen GmbH Moyen et procédé de détection d'analytes à l'aide de particules de granulés macroscopiques
CN107679286A (zh) * 2017-09-11 2018-02-09 广东昭信光电科技有限公司 一种实现led阵列均匀照明的透镜设计方法及控制系统
US20210060543A1 (en) * 2017-09-27 2021-03-04 Hewlett-Packard Development Company, L.P. Dilution dispensing
EP3470141B1 (fr) * 2017-10-11 2024-04-24 F. Hoffmann-La Roche AG Appareil et procédé de traitement d'un échantillon biologique avec des particules magnétiques
CA3079954A1 (fr) * 2017-11-02 2019-05-09 Memed Diagnostics Ltd. Cartouche et systeme pour analyser un liquide corporel
EP3710810B1 (fr) * 2017-11-14 2023-09-06 S.D. Sight Diagnostics Ltd. Porte-échantillon pour mesures optiques
GB201719769D0 (en) * 2017-11-28 2018-01-10 Cronin 3D Ltd Analytical device and methods of use
WO2019117366A1 (fr) * 2017-12-14 2019-06-20 (주)이노진 Dispositif de diagnostic in vitro basé sur le sang et procédé de diagnostic
EP3724636A4 (fr) 2017-12-15 2021-08-18 Evanostics, LLC Lecteur optique pour test d'analyte
US11255868B2 (en) 2018-02-12 2022-02-22 Electronics And Telecommunications Research Institute Fluid control equipment for bio-reaction, bio-reaction system and fluid control method for bio-reaction
JP7002637B2 (ja) * 2018-03-28 2022-01-20 富士フイルム株式会社 血液検査支援装置、血液検査支援システム、血液検査支援方法、及びプログラム
US11358148B2 (en) 2018-03-30 2022-06-14 Idexx Laboratories, Inc. Point-of-care diagnostic systems and containers for same
BR112020016080A2 (pt) 2018-03-30 2020-12-15 Idexx Laboratories, Inc. Sistema de diagnóstico médico no ponto de atendimento.
US11541396B2 (en) 2018-03-30 2023-01-03 Idexx Laboratories, Inc. Point-of-care diagnostic systems and containers for same
EP3788343B1 (fr) 2018-04-30 2024-03-27 Duke University Plateforme d'administration de médicament à base de polymère de type peg sensible aux stimuli
DE112019003251T5 (de) * 2018-06-25 2021-03-11 Vascu Technology, Inc. Verfahren und Kits zur Detektion von 11-Dehydro-Thromboxan B2
EP3819624A4 (fr) * 2018-07-03 2022-03-09 Shimadzu Corporation Outil d'assistance à l'extraction d'échantillons et procédé d'extraction d'échantillons
EP3829622A4 (fr) 2018-08-02 2022-05-11 Duke University Protéines de fusion à double agoniste
EP3608676B1 (fr) * 2018-08-08 2022-01-19 CTC Analytics AG Mettre l'échantillon dans le récipient de pointe de pipette pour un posttraitement
CN109223050B (zh) * 2018-08-23 2021-08-10 郑州大学第一附属医院 一种内分泌科临床抽检装置
USD888269S1 (en) 2018-09-02 2020-06-23 Memed Diagnostics Ltd. Capillary blood collector device
USD951482S1 (en) 2018-09-02 2022-05-10 Memed Diagnostics Ltd. Cartridge device
EP3644063B1 (fr) * 2018-10-23 2023-07-26 Roche Diagnostics GmbH Procédé de manipulation de contenants d'échantillons de laboratoire
EP3644064B1 (fr) * 2018-10-23 2021-08-18 Roche Diagnostics GmbH Procédé de manutention de conteneurs d'échantillons de laboratoire et appareil pour manipuler des conteneurs d'échantillons de laboratoire
CN109394241B (zh) * 2018-10-30 2022-07-08 宁静 一种医疗用内分泌科临床取检装置
KR102674662B1 (ko) 2018-11-14 2024-06-12 현대자동차주식회사 차량용 열교환기
TWI692777B (zh) * 2018-11-16 2020-05-01 長庚醫療財團法人高雄長庚紀念醫院 智能化急性腎損傷藥物警示系統
KR102178336B1 (ko) * 2018-11-27 2020-11-12 바디텍메드(주) 결핵 진단 방법 및 그 장치
CN109307541B (zh) * 2018-11-29 2020-03-24 郑州安图生物工程股份有限公司 一种发光板单孔残液的体积测量方法
CN109307540B (zh) * 2018-11-29 2020-04-21 郑州安图生物工程股份有限公司 一种酶标板单孔残液的体积测量方法
US12066383B2 (en) 2018-12-18 2024-08-20 Aspida Dx Inc. Optical analyte detection
WO2020142839A1 (fr) 2019-01-07 2020-07-16 1866402 Ontario Inc. Dispositif et procédés de séparation et d'analyse du sang
EP3911752B1 (fr) * 2019-01-14 2025-01-29 Infiniplex Ltd. Kit multi-test
EP3927468A1 (fr) 2019-02-18 2021-12-29 CTC Analytics AG Dispositif de distribution de fluide et procédé pour effectuer des dosages chimiques ou biologiques
DK3709024T3 (da) * 2019-03-12 2024-03-04 Radiometer Medical Aps Apparat til analyse af biologiske prøver
US20220143604A1 (en) * 2019-03-19 2022-05-12 Siemens Healthcare Diagnostics Inc. HBA1c ASSAY SLIDE AND METHOD OF MAKING SAME
CN110082519A (zh) * 2019-04-17 2019-08-02 迪瑞医疗科技股份有限公司 胱抑素c化学发光免疫检测试剂盒及其制备方法
CN110142068B (zh) * 2019-06-12 2024-02-02 杭州华得森生物技术有限公司 一种上皮间质混合型循环肿瘤细胞检测试剂盒及方法
US11512314B2 (en) 2019-07-12 2022-11-29 Duke University Amphiphilic polynucleotides
CN110376023B (zh) * 2019-07-26 2022-05-17 重庆德方信息技术有限公司 应用于智能马桶的控制系统及方法
CN114245873A (zh) * 2019-07-30 2022-03-25 匹思灵公司 同时分析多种生物标志物的设备和同时分析多种生物标志物的方法
KR102752778B1 (ko) * 2019-08-16 2025-01-14 한국전자통신연구원 바이오 물질 검출 방법
US20220266245A1 (en) * 2019-09-02 2022-08-25 Tan Tock Seng Hospital Pte Ltd A magnetic digital microfluidic system and method of performing an assay
US20230341422A1 (en) * 2019-09-27 2023-10-26 Epinex Diagnostics, Inc. A Home Test for Measuring Glucose Control and Kidney Function in Patients
CN114787685A (zh) 2019-12-12 2022-07-22 思迪赛特诊断有限公司 人工生成彩色血液涂片图像
CN113219192B (zh) * 2020-01-21 2023-10-20 深圳迎凯生物科技有限公司 反应器转移方法
WO2021150808A1 (fr) * 2020-01-23 2021-07-29 Precision Healing, Inc. Diagnostics de la peau utilisant des signatures optiques
CN111239430A (zh) * 2020-03-16 2020-06-05 中国科学院南京地理与湖泊研究所 一种批量处理样品的装置及方法
KR20220149602A (ko) * 2020-04-03 2022-11-08 (주)레보스케치 항원 맞춤형 검출시약이 프리로딩된 샌드위치 elisa용 카트리지 및 상기 카트리지를 이용한 샌드위치 elisa 장치
CN111504972B (zh) * 2020-05-21 2024-07-23 朱建国 一种pcr采样检测装置
CN115698680A (zh) * 2020-06-18 2023-02-03 挪威金田有限公司 确定全血样品血浆成分中分析物浓度的方法
US20220032288A1 (en) * 2020-07-29 2022-02-03 Smart Ink Technology Corp. Viral and biochemical early detection test kits
WO2022021377A1 (fr) * 2020-07-31 2022-02-03 杭州九洋生物科技有限公司 Pipette et procédé de pipetage
US11914131B1 (en) * 2020-08-16 2024-02-27 Gregory Dimitrenko Optical testing system for detecting infectious disease, testing device, specimen collector and related methods
CN112175808A (zh) * 2020-10-09 2021-01-05 张晓芬 一种用于检测血液病相关细胞突变的装置
WO2022101806A1 (fr) * 2020-11-11 2022-05-19 Diana Biotechnologies, S.R.O. Dispositif de prélèvement d'échantillons
WO2022123599A1 (fr) * 2020-12-08 2022-06-16 Varun Akur Venkatesan Système, procédé et dispositif de détection et de surveillance du syndrome des ovaires polykystiques
CN112932553B (zh) * 2021-02-01 2023-06-13 宁津县人民医院 一种用于妇科临床的阴道分泌物取样装置
CN114849805A (zh) * 2021-02-05 2022-08-05 苏州赛尼特格尔实验室科技有限公司 一种新型手动机械移液器
CA3233168A1 (fr) * 2021-09-27 2023-03-30 Richard D. Oleschuk Procede et appareil d'etalonnage rapide de spectrometrie de masse
US12226776B2 (en) 2021-11-04 2025-02-18 Instrumentation Laboratory Company Preparing substances in a medical diagnostic system
WO2023121101A1 (fr) * 2021-12-24 2023-06-29 한국과학기술원 Dispositif automatisé de diagnostic et procédé de diagnostic l'utilisant
USD981591S1 (en) 2022-05-05 2023-03-21 Singular Genomics Systems, Inc. Sample cartridge
USD979093S1 (en) 2022-05-05 2023-02-21 Singular Genomics Systems, Inc. Reagent cartridge
USD970036S1 (en) 2022-05-05 2022-11-15 Singular Genomics Systems, Inc. Reagent cartridge

Family Cites Families (898)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2398234A (en) 1942-12-11 1946-04-09 Horton & Converse Adjustable automatic pipette
US3600900A (en) 1969-11-03 1971-08-24 North American Rockwell Temperature controlled centrifuge
US3640434A (en) 1970-05-15 1972-02-08 Sherwood Medical Ind Inc Variable capacity fluid-dispensing device
US3696971A (en) 1970-09-24 1972-10-10 Electro Nucleonics Mechanism for simultaneously metering and dispensing liquids
US3756920A (en) 1971-04-30 1973-09-04 Nasa In biological samples my measuring light reactions automatic instrument for chemical processing to dedect microorganisms
GB1332207A (en) 1971-05-07 1973-10-03 Ass Elect Ind Apparatus for charged particle spectroscopy
BE793544A (fr) 1972-01-31 1973-04-16 American Hospital Supply Corp Centrifugeur
CA972183A (en) 1973-02-23 1975-08-05 Georges Revillet Microspectrophotometer
US3953172A (en) 1974-05-10 1976-04-27 Union Carbide Corporation Method and apparatus for assaying liquid materials
NL179870C (nl) 1974-08-16 1986-12-01 Sarstedt Kunststoff Vat voor het afnemen van bloed met een capillair mondstuk.
US4010893A (en) 1975-06-20 1977-03-08 Becton, Dickinson And Company Triac centrifuge
GB1562900A (en) 1975-09-24 1980-03-19 Aes Scient Ltd Preparation of blood plasma and serum samples
SU598649A1 (ru) 1976-05-04 1978-03-25 Предприятие П/Я В-2262 Центрифуга
US4087248A (en) 1976-07-26 1978-05-02 Miles Laughton E Multiple assay machine and method
US4269604A (en) * 1976-09-01 1981-05-26 Snowden Jr James E Method for the on-site determination of the presence of corrosive material in lubricating oil
US4157781A (en) 1978-07-19 1979-06-12 Hitoshi Maruyama Self balancing centrifuge
US4276383A (en) 1979-08-02 1981-06-30 The United States Of America As Represented By The Department Of Health, Education & Welfare Clot lysing timer
US4270921A (en) 1979-09-24 1981-06-02 Graas Joseph E Microchromatographic device and method for rapid determination of a desired substance
US4250830A (en) 1979-10-03 1981-02-17 Leif Robert C Swinging buckets
EP0030086B2 (fr) * 1979-11-13 1990-03-14 TECHNICON INSTRUMENTS CORPORATION (a New York corporation) Ensemble de tubes à essais, kit pour sa fabrication et procédé d'essais immunologiques manuels
US4276258A (en) 1980-01-28 1981-06-30 Coulter Electronics, Inc. Sample and stat feeding system and sample tray
US4362698A (en) 1980-03-07 1982-12-07 Sherman-Boosalis Corporation Closures for fluid sample cups
US4327595A (en) 1980-07-07 1982-05-04 Hamilton Company Method and apparatus for simultaneous dilution and dispensation
US4344563A (en) 1980-12-23 1982-08-17 E. I. Du Pont De Nemours And Company Centrifuge rotor having vertically offset trunnion pins
FR2498331A1 (fr) * 1981-01-20 1982-07-23 Kadouche Jean Recipient reactif pour analyse notamment immunologique
JPS5822254B2 (ja) 1981-07-03 1983-05-07 株式会社 久保田製作所 遠心分離機用ロ−タ
US4488814A (en) 1981-09-28 1984-12-18 Miles Laboratories, Inc. Apparatus for and method of optical absorbance and fluorescent radiation measurement
US4486315A (en) 1982-03-11 1984-12-04 Ortho Diagnostic Systems Inc. Immunoassay microparticle washing system and method of use
US4437586A (en) 1982-03-29 1984-03-20 Eastman Kodak Company Mechanically actuated pipette dispenser
US4478094A (en) 1983-01-21 1984-10-23 Cetus Corporation Liquid sample handling system
US4816567A (en) 1983-04-08 1989-03-28 Genentech, Inc. Recombinant immunoglobin preparations
US4554839A (en) 1983-10-14 1985-11-26 Cetus Corporation Multiple trough vessel for automated liquid handling apparatus
US4555957A (en) 1983-10-14 1985-12-03 Cetus Corporation Bi-directional liquid sample handling system
US5171534A (en) 1984-01-16 1992-12-15 California Institute Of Technology Automated DNA sequencing technique
US4952518A (en) 1984-10-01 1990-08-28 Cetus Corporation Automated assay machine and assay tray
US4545497A (en) 1984-11-16 1985-10-08 Millipore Corporation Container cap with frangible septum
DE185330T1 (de) 1984-12-18 1986-11-27 Cetus Corp., Emeryville, Calif. System zur behandlung mehrfacher proben.
JPS61202142A (ja) 1985-03-06 1986-09-06 Teijin Ltd 吸光度を用いた分析方法および分析装置
JPS61202141A (ja) 1985-03-06 1986-09-06 Nec Corp 吸光光度計
US4593837A (en) 1985-03-15 1986-06-10 Eastman Kodak Company Variable volume pipette
US4683195A (en) 1986-01-30 1987-07-28 Cetus Corporation Process for amplifying, detecting, and/or-cloning nucleic acid sequences
JPS61254833A (ja) 1985-05-08 1986-11-12 Toyo Soda Mfg Co Ltd 液定量取出し装置
US4756884A (en) 1985-08-05 1988-07-12 Biotrack, Inc. Capillary flow device
JPS6247555A (ja) 1985-08-23 1987-03-02 エフ．ホフマン　―　ラ　ロシュ　アーゲー シンチレ−シヨン近接定量法
US4725406A (en) * 1985-10-21 1988-02-16 American Bionetics, Inc. Apparatus and method for diagnostic analysis of biological fluids
DE3614085A1 (de) 1985-12-12 1987-06-19 Hirschmann Glasgeraete Pipette
CH671526A5 (fr) 1985-12-17 1989-09-15 Hamilton Bonaduz Ag
JPH0652227B2 (ja) 1986-04-25 1994-07-06 梅谷 陽二 微小注入量測定装置
GB2190195A (en) * 1986-05-09 1987-11-11 Cambridge Life Sciences Microtitre plate reader
JPH0727700Y2 (ja) 1986-06-16 1995-06-21 日本電気株式会社 Ｐｌｌシンセサイザの制御回路
US4744955A (en) 1986-08-08 1988-05-17 Shapiro Justin J Adjustable volume pipette sampler
US5322770A (en) 1989-12-22 1994-06-21 Hoffman-Laroche Inc. Reverse transcription with thermostable DNA polymerases - high temperature reverse transcription
US5310652A (en) 1986-08-22 1994-05-10 Hoffman-La Roche Inc. Reverse transcription with thermostable DNA polymerase-high temperature reverse transcription
JPH0816675B2 (ja) 1986-09-26 1996-02-21 株式会社島津製作所 ガスクロマトグラフ装置
JPH07119769B2 (ja) 1986-10-01 1995-12-20 株式会社日立製作所 自動分析装置
US4933291A (en) 1986-12-22 1990-06-12 Eastman Kodak Company Centrifugable pipette tip and pipette therefor
US4902969A (en) 1987-06-01 1990-02-20 Reliability Incorporated Automated burn-in system
JPH0697231B2 (ja) 1987-07-15 1994-11-30 富士写真フイルム株式会社 生化学分析装置
US4822331A (en) 1987-11-09 1989-04-18 Taylor David C Centrifuge
US5055263A (en) 1988-01-14 1991-10-08 Cyberlab, Inc. Automated pipetting system
US5130238A (en) 1988-06-24 1992-07-14 Cangene Corporation Enhanced nucleic acid amplification process
US4925629A (en) * 1988-07-28 1990-05-15 Bioquant, Inc. Diagnostic device
ATE134040T1 (de) * 1988-08-02 1996-02-15 Abbott Lab Verfahren und vorrichtung zum erzeugen von eichdaten für die analyse
US5320808A (en) 1988-08-02 1994-06-14 Abbott Laboratories Reaction cartridge and carousel for biological sample analyzer
US5281540A (en) * 1988-08-02 1994-01-25 Abbott Laboratories Test array for performing assays
JPH0275959A (ja) 1988-09-12 1990-03-15 Nittec Co Ltd 自動分折装置
US5186162A (en) 1988-09-14 1993-02-16 Interpore Orthopaedics, Inc. Ultrasonic transducer device for treatment of living tissue and/or cells
US5530101A (en) 1988-12-28 1996-06-25 Protein Design Labs, Inc. Humanized immunoglobulins
US5326445A (en) * 1989-05-01 1994-07-05 Hewlett-Packard Company Vacuum injection capillary electrophoresis
EP0423278B2 (fr) 1989-05-01 1998-04-15 Rhone-Poulenc Viscosuisse Sa Procede pour la fabrication de monofilaments fins
WO1990013668A1 (fr) 1989-05-05 1990-11-15 Lifecodes Corporation Methode pour l'analyse genetique d'un echantillon d'acide nucleique
ATE141956T1 (de) 1989-07-11 1996-09-15 Gen Probe Inc Verfahren zur vervielfältigung von nukleinsäuresequenzen
CA2020958C (fr) 1989-07-11 2005-01-11 Daniel L. Kacian Methodes d'amplification de sequences d'acide nucleique
US5683888A (en) 1989-07-22 1997-11-04 University Of Wales College Of Medicine Modified bioluminescent proteins and their use
IL94212A0 (en) 1989-07-24 1991-01-31 Tri Tech Partners And Triton B Automated analytical apparatus and method
US5061449A (en) 1989-07-25 1991-10-29 Matrix Technologies, Corp. Expandable multi-channel pipetter
US5005981A (en) 1989-09-08 1991-04-09 Becton, Dickinson And Company Apparatus for method for causing vortices in a test tube
US4991433A (en) * 1989-09-21 1991-02-12 Applied Acoustic Research Phase track system for monitoring fluid material within a container
US5072382A (en) 1989-10-02 1991-12-10 Kamentsky Louis A Methods and apparatus for measuring multiple optical properties of biological specimens
US5089229A (en) 1989-11-22 1992-02-18 Vettest S.A. Chemical analyzer
JP2731613B2 (ja) * 1989-12-12 1998-03-25 株式会社クラレ 酵素免疫測定用カートリツジ、それを用いた測定方法及び測定装置
US5859205A (en) 1989-12-21 1999-01-12 Celltech Limited Humanised antibodies
US5292658A (en) 1989-12-29 1994-03-08 University Of Georgia Research Foundation, Inc. Boyd Graduate Studies Research Center Cloning and expressions of Renilla luciferase
SU1722603A1 (ru) 1990-01-02 1992-03-30 Специальное конструкторское бюро биофизической аппаратуры Московского научно-производственного объединения "Биофизприбор" Центрифуга
TW199858B (fr) 1990-03-30 1993-02-11 Fujirebio Kk
US5061381A (en) 1990-06-04 1991-10-29 Abaxis, Inc. Apparatus and method for separating cells from biological fluids
US5173193A (en) 1991-04-01 1992-12-22 Schembri Carol T Centrifugal rotor having flow partition
US5122284A (en) 1990-06-04 1992-06-16 Abaxis, Inc. Apparatus and method for optically analyzing biological fluids
US5242606A (en) 1990-06-04 1993-09-07 Abaxis, Incorporated Sample metering port for analytical rotor having overflow chamber
DK0533838T3 (da) 1990-06-11 1998-02-23 Nexstar Pharmaceuticals Inc Nukleinsyreligander
US5270163A (en) 1990-06-11 1993-12-14 University Research Corporation Methods for identifying nucleic acid ligands
US5527670A (en) 1990-09-12 1996-06-18 Scientific Generics Limited Electrochemical denaturation of double-stranded nucleic acid
EP0478319B1 (fr) 1990-09-28 1997-04-02 Kabushiki Kaisha Toshiba Méthode pour la détection de gènes
JP2969935B2 (ja) 1990-11-30 1999-11-02 東ソー株式会社 液定量取出し装置
DE4041905A1 (de) 1990-12-27 1992-07-02 Boehringer Mannheim Gmbh Testtraeger-analysesystem
US5455166A (en) 1991-01-31 1995-10-03 Becton, Dickinson And Company Strand displacement amplification
FR2673183B1 (fr) 1991-02-21 1996-09-27 Asulab Sa Complexes mono, bis ou tris (2,2'-bipyridine substituee) d'un metal choisi parmi le fer, le ruthenium, l'osmium ou le vanadium et leurs procedes de preparation .
US5273905A (en) 1991-02-22 1993-12-28 Amoco Corporation Processing of slide mounted material
JP3126980B2 (ja) 1991-03-11 2001-01-22 ザ・ユニバーシテイ・オブ・ジヨージア・リサーチ・フアウンデーシヨン・インコーポレーテツド レニラ（ｒｅｎｉｌｌａ）ルシフェラーゼのクローニング及び発現
US5264184A (en) 1991-03-19 1993-11-23 Minnesota Mining And Manufacturing Company Device and a method for separating liquid samples
US5230864A (en) 1991-04-10 1993-07-27 Eastman Kodak Company Gravity assisted collection device
US5112574A (en) 1991-04-26 1992-05-12 Imanigation, Ltd. Multititer stopper array for multititer plate or tray
US5324481A (en) * 1991-06-03 1994-06-28 Abbott Laboratories Carousel for assay specimen carrier
DE122004000008I1 (de) 1991-06-14 2005-06-09 Genentech Inc Humanisierter Heregulin Antikörper.
WO1994004679A1 (fr) 1991-06-14 1994-03-03 Genentech, Inc. Procede pour fabriquer des anticorps humanises
FR2679661B1 (fr) 1991-07-26 1994-10-14 Sfri Appareil d'analyse automatique d'echantillons.
US5266272A (en) 1991-10-31 1993-11-30 Baxter Diagnostics Inc. Specimen processing and analyzing systems with a station for holding specimen trays during processing
EP0541340B1 (fr) 1991-11-05 1997-07-16 The Perkin-Elmer Corporation Appareillage et procédé pour le synthèse des biopolymères
US6136535A (en) * 1991-11-14 2000-10-24 Digene Corporation Continuous amplification reaction
US5270184A (en) 1991-11-19 1993-12-14 Becton, Dickinson And Company Nucleic acid target generation
US5960160A (en) 1992-03-27 1999-09-28 Abbott Laboratories Liquid heater assembly with a pair temperature controlled electric heating elements and a coiled tube therebetween
US5507410A (en) 1992-03-27 1996-04-16 Abbott Laboratories Meia cartridge feeder
US5288390A (en) 1992-03-30 1994-02-22 Sun Company, Inc. (R&M) Polycyclic aromatic ring cleavage (PARC) process
WO1993019827A1 (fr) 1992-04-02 1993-10-14 Abaxis, Inc. Rotor d'analyse comportant une chambre de melange de colorants
DE69303483T2 (de) 1992-05-01 1997-02-06 Univ Pennsylvania Mikrohergestellte Vorrichtungen zum Handhaben von Sperma
US5380487A (en) 1992-05-05 1995-01-10 Pasteur Sanofi Diagnostics Device for automatic chemical analysis
US5357953A (en) 1992-05-21 1994-10-25 Puritan-Bennett Corporation Measurement device and method of calibration
DE69334326D1 (de) 1992-09-14 2010-05-20 Stanford Res Inst Int Hochkonvertierende Reportermoleküle für biologische und andere Testverfahren unter Verwendung von Laseranregungstechniken
US5674698A (en) 1992-09-14 1997-10-07 Sri International Up-converting reporters for biological and other assays using laser excitation techniques
EP0619476B1 (fr) 1992-12-19 1999-09-22 Boehringer Mannheim Gmbh Dispositif pour la détection d'un interface fluidique dans un tube de mesure transparent
DE4305581A1 (de) 1993-02-24 1994-08-25 Hettich Andreas Fa Rotor für eine Schwenkbecherzentrifuge
FI96143C (fi) * 1993-03-16 1996-05-10 Wallac Oy Biospesifinen määritysmenetelmä
US5416879A (en) 1993-03-29 1995-05-16 World Precision Instruments, Inc. Apparatus and method for measuring light absorption in small aqueous fluid samples
US5478750A (en) 1993-03-31 1995-12-26 Abaxis, Inc. Methods for photometric analysis
JP3563140B2 (ja) 1995-01-19 2004-09-08 株式会社日立製作所 キャピラリーアレイ電気泳動装置
EP0702728B1 (fr) 1993-06-09 1998-04-15 Gamera Bioscience Corporation Reaction de cycle magnetique
US5578269A (en) 1993-06-11 1996-11-26 Ortho Diagnostic Systems Inc. Automated blood analysis system with an integral centrifuge
DE69430152T2 (de) 1993-06-25 2002-10-31 Edward W. Stark Verfahren und Vorrichtung zum Messen von Glukoseverwandten Substanzen
JP3343156B2 (ja) 1993-07-14 2002-11-11 アークレイ株式会社 光学式成分濃度測定装置および方法
GB9315671D0 (en) 1993-07-29 1993-09-15 Dow Corning Sa Foam control agents and their use
ITMI931761A1 (it) 1993-08-03 1995-02-03 Healtech Sa Dispositivo di supporto di informazioni associabile a pazienti ambulatoriali o ospedalieri per la loro identificazione automatica ed
TW265262B (en) 1993-08-13 1995-12-11 Nat Science Committee Mother-and-child interconnected centrifuge tube used for solution separation
DK0713533T3 (da) * 1993-08-13 2002-11-04 Albany Molecular Res Inc Biokatalytiske metoder til syntese og identifikation af biologisk aktive forbindelser
WO1995006240A1 (fr) 1993-08-24 1995-03-02 Metrika Laboratories, Inc. Nouveau dispositif electronique d'analyse jetable
CA2129787A1 (fr) 1993-08-27 1995-02-28 Russell G. Higuchi Surveillance de plusieurs reactions d'amplification simultanement et analyse de ces reactions simultanement
US5397709A (en) 1993-08-27 1995-03-14 Becton Dickinson And Company System for detecting bacterial growth in a plurality of culture vials
US5591643A (en) 1993-09-01 1997-01-07 Abaxis, Inc. Simplified inlet channels
US6235531B1 (en) 1993-09-01 2001-05-22 Abaxis, Inc. Modified siphons for improved metering precision
JPH0783936A (ja) 1993-09-10 1995-03-31 Taitetsuku Kk 理化学実験方法
US6146826A (en) 1993-09-10 2000-11-14 The Trustees Of Columbia University In The City Of New York Green fluorescent protein
AU7843194A (en) * 1993-09-24 1995-04-10 Abbott Laboratories Automated continuous and random access analytical system and components thereof
JP3391862B2 (ja) 1993-10-05 2003-03-31 株式会社日立製作所 クロマトグラム解析方法
JPH07120393A (ja) 1993-10-13 1995-05-12 Nippon Tectron Co Ltd 蛍光検出法
US5525300A (en) 1993-10-20 1996-06-11 Stratagene Thermal cycler including a temperature gradient block
EP0892445B1 (fr) 1993-11-02 2004-04-07 Matsushita Electric Industrial Co., Ltd. Dispositif semiconducteur comprenant un agrégat de micro-aiguilles semi-conductrices
US5403415A (en) 1993-11-17 1995-04-04 Abaxis, Inc. Method and device for ultrasonic welding
JPH07151101A (ja) 1993-11-29 1995-06-13 Kazuo Sugimura ダイヤフラム接触面が渦巻状の容器
JPH07196314A (ja) 1993-12-28 1995-08-01 Maruo Calcium Co Ltd チューブ状合成無機微粒子
WO1995021191A1 (fr) 1994-02-04 1995-08-10 William Ward Indicateur bioluminescent fonde sur l'expression d'un gene codant pour une proteine modifiee a fluorescence verte
US5551241A (en) 1994-03-02 1996-09-03 Boeckel; John W. Thermoelectric cooling centrifuge
EP0750680B1 (fr) 1994-03-15 1999-01-13 Scientific Generics Ltd Denaturation electro-chimique de l'acide nucleique double brins
US5590052A (en) 1994-04-14 1996-12-31 Abaxis, Inc. Error checking in blood analyzer
US5648211A (en) 1994-04-18 1997-07-15 Becton, Dickinson And Company Strand displacement amplification using thermophilic enzymes
CA2147560A1 (fr) 1994-04-22 1995-10-23 Donald H. Devaughn Appareil avec haut de pipette resistant au transfert de liquide et d'aerosol; methode de reduction de transfert
US5483799A (en) 1994-04-29 1996-01-16 Dalto; Michael Temperature regulated specimen transporter
JP3584990B2 (ja) 1994-05-09 2004-11-04 タカラバイオ株式会社 抗ヒトインフルエンザウイルス抗体
US5976896A (en) * 1994-06-06 1999-11-02 Idexx Laboratories, Inc. Immunoassays in capillary tubes
US6403367B1 (en) 1994-07-07 2002-06-11 Nanogen, Inc. Integrated portable biological detection system
JP2637695B2 (ja) 1994-07-12 1997-08-06 株式会社バイオセンサー研究所 溶液吸引器具および吸引式溶液内微量物質測定装置
US5639428A (en) 1994-07-19 1997-06-17 Becton Dickinson And Company Method and apparatus for fully automated nucleic acid amplification, nucleic acid assay and immunoassay
DE69536004D1 (de) 1994-07-25 2009-10-29 Molecular Devices Corp Bestimmung der optischen absorptions-weglänge in einem vertikalstrahlphotometer
US5891734A (en) 1994-08-01 1999-04-06 Abbott Laboratories Method for performing automated analysis
US5527257A (en) 1994-09-14 1996-06-18 Piramoon Technologies, Inc. Rotor having endless straps for mounting swinging buckets
JP3403839B2 (ja) * 1994-10-27 2003-05-06 プレシジョン・システム・サイエンス株式会社 カートリッジ容器
JP3652424B2 (ja) * 1994-10-27 2005-05-25 日本政策投資銀行 自動分析装置及びその方法
US5777079A (en) 1994-11-10 1998-07-07 The Regents Of The University Of California Modified green fluorescent proteins
JP3571092B2 (ja) * 1994-12-20 2004-09-29 富士写真フイルム株式会社 乾式分析フィルム片への試料液点着方法
US5932110A (en) * 1995-02-13 1999-08-03 Aksys, Ltd. Dialysate conductivity adjustment in a batch dialysate preparation system
US6484897B1 (en) 1995-02-13 2002-11-26 Amcad Holdings Limited Containers with variable volume
US5557596A (en) 1995-03-20 1996-09-17 Gibson; Gary Ultra-high density storage device
US5578270A (en) 1995-03-24 1996-11-26 Becton Dickinson And Company System for nucleic acid based diagnostic assay
US5874214A (en) 1995-04-25 1999-02-23 Irori Remotely programmable matrices with memories
US6340588B1 (en) 1995-04-25 2002-01-22 Discovery Partners International, Inc. Matrices with memories
US6352854B1 (en) 1995-04-25 2002-03-05 Discovery Partners International, Inc. Remotely programmable matrices with memories
US5582705A (en) 1995-05-19 1996-12-10 Iowa State University Research Foundation, Inc. Multiplexed capillary electrophoresis system
US5772962A (en) 1995-05-29 1998-06-30 Hitachi, Ltd. Analyzing apparatus using disposable reaction vessels
US5518923A (en) 1995-06-06 1996-05-21 Becton Dickinson And Company Compact blood culture apparatus
JP3839524B2 (ja) 1995-06-07 2006-11-01 アジレント・テクノロジーズ・インク 小型化全分析システム
US6274288B1 (en) 1995-06-12 2001-08-14 California Institute Of Technology Self-trapping and self-focusing of optical beams in photopolymers
US6168948B1 (en) 1995-06-29 2001-01-02 Affymetrix, Inc. Miniaturized genetic analysis systems and methods
JP3927570B2 (ja) * 1995-07-31 2007-06-13 プレシジョン・システム・サイエンス株式会社 容器
EP2259070A3 (fr) 1995-07-31 2011-03-30 Precision System Science Co., Ltd. Récipient
JPH0968533A (ja) 1995-08-31 1997-03-11 Brother Ind Ltd 薬品投与量を表示可能な生化学物質測定装置
JP3515646B2 (ja) 1995-09-18 2004-04-05 大塚電子株式会社 マルチキャピラリ電気泳動装置
DE19535046C2 (de) 1995-09-21 1998-04-16 Eppendorf Geraetebau Netheler Handgerät zum Pipettieren und photometrischen Messen von Proben
US5628890A (en) 1995-09-27 1997-05-13 Medisense, Inc. Electrochemical sensor
JPH09113511A (ja) 1995-10-18 1997-05-02 Kdk Corp グリコアルブミン測定用乾式試験片
US5687716A (en) 1995-11-15 1997-11-18 Kaufmann; Peter Selective differentiating diagnostic process based on broad data bases
US5854033A (en) 1995-11-21 1998-12-29 Yale University Rolling circle replication reporter systems
US20060074063A1 (en) 1995-12-29 2006-04-06 Fernandez-Pol Jose A Pharmacological agent and method of treatment
US6660233B1 (en) 1996-01-16 2003-12-09 Beckman Coulter, Inc. Analytical biochemistry system with robotically carried bioarray
JPH09192218A (ja) 1996-01-16 1997-07-29 Hitachi Ltd 血糖値管理システム
US5874304A (en) 1996-01-18 1999-02-23 University Of Florida Research Foundation, Inc. Humanized green fluorescent protein genes and methods
US5863502A (en) 1996-01-24 1999-01-26 Sarnoff Corporation Parallel reaction cassette and associated devices
CN1096185C (zh) 1996-01-27 2002-12-11 三星电子株式会社 使用运动和空间相关的隔行向逐行转换装置和方法
US5804387A (en) 1996-02-01 1998-09-08 The Board Of Trustees Of The Leland Stanford Junior University FACS-optimized mutants of the green fluorescent protein (GFP)
US5876995A (en) 1996-02-06 1999-03-02 Bryan; Bruce Bioluminescent novelty items
US5670375A (en) 1996-02-21 1997-09-23 Biomerieux Vitek, Inc. Sample card transport method for biological sample testing machine
US20010044588A1 (en) 1996-02-22 2001-11-22 Mault James R. Monitoring system
JP2988362B2 (ja) 1996-03-11 1999-12-13 株式会社日立製作所 多検体分析システム
JPH09244055A (ja) 1996-03-14 1997-09-19 Hitachi Ltd 液晶表示装置
DE19610538A1 (de) 1996-03-18 1997-09-25 Deutsches Krebsforsch Strahlungsermittlungsvorrichtung
EP0888546A1 (fr) * 1996-03-19 1999-01-07 University Of Utah Research Foundation Appareil d'oscillation et methodes d'immunodosage fluorescent homogene a plusieurs echantillons a analyser
US6114122A (en) 1996-03-26 2000-09-05 Affymetrix, Inc. Fluidics station with a mounting system and method of using
JP2783277B2 (ja) 1996-03-27 1998-08-06 日本電気株式会社 患者監視装置及び患者監視システム
ATE315225T1 (de) * 1996-03-29 2006-02-15 Byk Gulden Italia Spa Automatische diagnosevorrichtung
US5906795A (en) 1996-04-08 1999-05-25 Sanyo Electric Co., Ltd. Pipetting apparatus
JPH09281078A (ja) 1996-04-09 1997-10-31 Hitachi Electron Eng Co Ltd Ｄｎａ塩基配列決定装置
US5896297A (en) 1996-04-15 1999-04-20 Valerino, Sr.; Fred M. Robotube delivery system
US6399023B1 (en) 1996-04-16 2002-06-04 Caliper Technologies Corp. Analytical system and method
US5942443A (en) 1996-06-28 1999-08-24 Caliper Technologies Corporation High throughput screening assay systems in microscale fluidic devices
US5885470A (en) 1997-04-14 1999-03-23 Caliper Technologies Corporation Controlled fluid transport in microfabricated polymeric substrates
JP3213566B2 (ja) 1996-04-26 2001-10-02 アークレイ株式会社 検体分析用具およびそれを用いた検体分析方法並びに検体分析装置
US5851170A (en) 1996-04-30 1998-12-22 Dade Behring Inc. Centrifuge with cam selectable rotational angles and method for unloading same
US5879628A (en) 1996-05-06 1999-03-09 Helena Laboratories Corporation Blood coagulation system having a bar code reader and a detecting means for detecting the presence of reagents in the cuvette
JP3682302B2 (ja) * 1996-05-20 2005-08-10 プレシジョン・システム・サイエンス株式会社 分注機による磁性体粒子の制御方法およびその装置
US5980830A (en) 1996-05-20 1999-11-09 Sendx Medical, Inc. Portable modular blood analyzer with simplified fluid handling sequence
IL118432A (en) 1996-05-27 1999-12-31 Yissum Res Dev Co Electrochemical and photochemical electrodes and their use
AU727296B2 (en) 1996-06-04 2000-12-07 University Of Utah Research Foundation System and methods for monitoring for DNA amplification by fluorescence
US5939291A (en) 1996-06-14 1999-08-17 Sarnoff Corporation Microfluidic method for nucleic acid amplification
US6429025B1 (en) 1996-06-28 2002-08-06 Caliper Technologies Corp. High-throughput screening assay systems in microscale fluidic devices
US5797898A (en) 1996-07-02 1998-08-25 Massachusetts Institute Of Technology Microchip drug delivery devices
US5807523A (en) 1996-07-03 1998-09-15 Beckman Instruments, Inc. Automatic chemistry analyzer
AU3651497A (en) 1996-07-05 1998-02-02 Beckman Coulter, Inc. Automated sample processing system
EP0818547A1 (fr) 1996-07-10 1998-01-14 Autoliv ASP, Inc. Récupération de métaux à partir de dispositifs "air bag"
US5925558A (en) 1996-07-16 1999-07-20 The Regents Of The University Of California Assays for protein kinases using fluorescent protein substrates
US6145688A (en) 1996-07-17 2000-11-14 Smith; James C. Closure device for containers
US5915284A (en) 1996-07-22 1999-06-22 Cyberlab, Inc. Multiple channel pipetting device
US6101488A (en) 1996-09-04 2000-08-08 Fujitsu Limited Intelligent information program generation and retrieval system
US5854684A (en) 1996-09-26 1998-12-29 Sarnoff Corporation Massively parallel detection
GB9620209D0 (en) 1996-09-27 1996-11-13 Cemu Bioteknik Ab Method of sequencing DNA
US5976796A (en) 1996-10-04 1999-11-02 Loma Linda University Construction and expression of renilla luciferase and green fluorescent protein fusion genes
JPH10123136A (ja) 1996-10-24 1998-05-15 Nippon Tectron Co Ltd 自動免疫分析装置
US5874046A (en) 1996-10-30 1999-02-23 Raytheon Company Biological warfare agent sensor system employing ruthenium-terminated oligonucleotides complementary to target live agent DNA sequences
JP3390793B2 (ja) 1996-11-06 2003-03-31 日本電信電話株式会社 曲げ剛性測定方法及びその装置
AU746549B2 (en) 1996-11-20 2002-05-02 Becton Dickinson & Company Microfabricated isothermal nucleic acid amplification devices and methods
GB9624096D0 (en) 1996-11-20 1997-01-08 Microbial Systems Ltd Apparatus and method of use thereof
US6093156A (en) 1996-12-06 2000-07-25 Abbott Laboratories Method and apparatus for obtaining blood for diagnostic tests
EP1015872B1 (fr) 1996-12-12 2005-03-02 Prolume, Ltd. Appareil permettant de detecter et d'identifier des agents infectieux et procede correspondant
JPH10239240A (ja) 1997-02-25 1998-09-11 Hitachi Ltd 自動ｄｎａプローブ装置
GB2337113B (en) 1997-02-28 2001-03-21 Burstein Lab Inc Laboratory in a disk
US8293064B2 (en) 1998-03-02 2012-10-23 Cepheid Method for fabricating a reaction vessel
WO1998038487A2 (fr) 1997-02-28 1998-09-03 Cepheid Ensemble pour reaction chimique avec echange thermique et interrogee optiquement
US5846492A (en) 1997-03-11 1998-12-08 Johnson & Johnson Clinical Diagnostics, Inc. Sample quality measurement and/or analyte measurement in the dispensing tip of an analyzer
US6013528A (en) 1997-03-11 2000-01-11 Ortho-Clinical Diagnostis, Inc. Analyzer throughput featuring through-the-tip analysis
JP3393361B2 (ja) 1997-03-24 2003-04-07 国立身体障害者リハビリテーションセンター総長 バイオセンサ
GB9706654D0 (en) 1997-04-02 1997-05-21 Scient Generics Ltd Disassociation of interacting molecules
US6235471B1 (en) 1997-04-04 2001-05-22 Caliper Technologies Corp. Closed-loop biochemical analyzers
EP0917590A1 (fr) 1997-04-04 1999-05-26 Innogenetics N.V. Amplification isothermique en chaine par polymerase par oscillation controlee de la concentration d'ions metalliques divalents
US5961451A (en) 1997-04-07 1999-10-05 Motorola, Inc. Noninvasive apparatus having a retaining member to retain a removable biosensor
US6696286B1 (en) * 1997-04-09 2004-02-24 3M Innovative Properties Company Method and devices for detecting and enumerating microorganisms
EP0871034B1 (fr) 1997-04-10 2007-03-07 Hitachi, Ltd. Appareil d'analyses automatisé
JP3181853B2 (ja) 1997-04-10 2001-07-03 キヤノン株式会社 密着型イメージセンサ及び情報処理装置
DE19717023C2 (de) 1997-04-23 2003-02-06 Micronas Gmbh Vorrichtung zum Behandeln von malignen, tumorösen Gewebebereichen
KR100351531B1 (ko) 1997-04-25 2002-09-11 캘리퍼 테크놀로지스 코포레이션 기하형상이 개선된 채널을 채용하는 미소 유체 장치
US6429007B1 (en) 1997-05-02 2002-08-06 BIOMéRIEUX, INC. Nucleic acid amplification reaction station for disposable test devices
US6406845B1 (en) 1997-05-05 2002-06-18 Trustees Of Tuft College Fiber optic biosensor for selectively detecting oligonucleotide species in a mixed fluid sample
JPH10305016A (ja) 1997-05-08 1998-11-17 Casio Comput Co Ltd 行動情報提供システム
US5904899A (en) 1997-05-15 1999-05-18 Tosoh Corporation Assaying apparatus and a vessel holder device in use with the assaying apparatus
US5985214A (en) 1997-05-16 1999-11-16 Aurora Biosciences Corporation Systems and methods for rapidly identifying useful chemicals in liquid samples
ATE306324T1 (de) * 1997-06-09 2005-10-15 Hoffmann La Roche Einweg-analysevorrichtung
US6115545A (en) 1997-07-09 2000-09-05 Hewlett-Packard Company Automatic internet protocol (IP) address allocation and assignment
WO1999004043A1 (fr) 1997-07-14 1999-01-28 Abbott Laboratories Telemedecine
US7475965B2 (en) 1997-07-15 2009-01-13 Silverbrook Research Pty Ltd Inkjet printer with low droplet to chamber volume ratio
US6589789B1 (en) 1997-07-21 2003-07-08 Quest Diagnostics Incorporated Automated centrifuge loading device
JPH1137845A (ja) 1997-07-22 1999-02-12 Matsushita Electric Ind Co Ltd 血清量測定装置
US5876675A (en) 1997-08-05 1999-03-02 Caliper Technologies Corp. Microfluidic devices and systems
US6294331B1 (en) 1997-08-08 2001-09-25 The United States Of America As Represented By The Department Of Health And Human Services Methods for assessing genetic and phenotypic markers by simultaneous multicolor visualization of chromogenic dyes using brightfield microscopy and spectral imaging
US6368871B1 (en) 1997-08-13 2002-04-09 Cepheid Non-planar microstructures for manipulation of fluid samples
JPH1157560A (ja) 1997-08-27 1999-03-02 Shin Meiwa Ind Co Ltd 液体散布車
US6042909A (en) 1997-09-03 2000-03-28 Circe Biomedical, Inc. Encapsulation device
EP0902290B1 (fr) 1997-09-11 2008-11-05 Hitachi, Ltd. Système de manipulation d'échantillons pour des dispositifs d'analyse automatiques
US6597450B1 (en) * 1997-09-15 2003-07-22 Becton, Dickinson And Company Automated Optical Reader for Nucleic Acid Assays
GB9719673D0 (en) * 1997-09-17 1997-11-19 Glaxo Group Ltd Novel apparatus
US6825921B1 (en) 1999-11-10 2004-11-30 Molecular Devices Corporation Multi-mode light detection system
US6902703B2 (en) 1999-05-03 2005-06-07 Ljl Biosystems, Inc. Integrated sample-processing system
US6982431B2 (en) 1998-08-31 2006-01-03 Molecular Devices Corporation Sample analysis systems
US5842787A (en) 1997-10-09 1998-12-01 Caliper Technologies Corporation Microfluidic systems incorporating varied channel dimensions
DE19745373A1 (de) * 1997-10-14 1999-04-15 Bayer Ag Optisches Meßsystem zur Erfassung von Lumineszenz- oder Fluoreszenzsignalen
FI107080B (fi) 1997-10-27 2001-05-31 Nokia Mobile Phones Ltd Mittauslaite
US6121054A (en) * 1997-11-19 2000-09-19 Trega Biosciences, Inc. Method for separation of liquid and solid phases for solid phase organic syntheses
US6174675B1 (en) 1997-11-25 2001-01-16 Caliper Technologies Corp. Electrical current for controlling fluid parameters in microchannels
AUPP058197A0 (en) 1997-11-27 1997-12-18 A.I. Scientific Pty Ltd Pathology sample tube distributor
US6083682A (en) * 1997-12-19 2000-07-04 Glaxo Group Limited System and method for solid-phase parallel synthesis of a combinatorial collection of compounds
DE69840916D1 (de) * 1997-12-22 2009-07-30 Roche Diagnostics Operations Messgerät
ATE400358T1 (de) 1997-12-24 2008-07-15 Cepheid Vorrichtung und verfahren zur lyse
US6074616A (en) 1998-01-05 2000-06-13 Biosite Diagnostics, Inc. Media carrier for an assay device
US5993417A (en) * 1998-01-06 1999-11-30 Yerfino; Daniel Alberto Disposable syringe with an automatically retractable hypodermic needle
US5972615A (en) * 1998-01-21 1999-10-26 Urocor, Inc. Biomarkers and targets for diagnosis, prognosis and management of prostate disease
WO1999039829A1 (fr) * 1998-02-04 1999-08-12 Merck & Co., Inc. Puits virtuels destines a etre utilises dans des criblages a haut rendement
US6420143B1 (en) * 1998-02-13 2002-07-16 Caliper Technologies Corp. Methods and systems for performing superheated reactions in microscale fluidic systems
US6861035B2 (en) 1998-02-24 2005-03-01 Aurora Discovery, Inc. Multi-well platforms, caddies, lids and combinations thereof
US6369893B1 (en) 1998-05-19 2002-04-09 Cepheid Multi-channel optical detection system
US6030582A (en) 1998-03-06 2000-02-29 Levy; Abner Self-resealing, puncturable container cap
US20110130740A1 (en) 1998-03-06 2011-06-02 Abner Levy Medication Bottle for Use with Oral Syringe
US6752965B2 (en) 1998-03-06 2004-06-22 Abner Levy Self resealing elastomeric closure
WO1999046591A2 (fr) 1998-03-10 1999-09-16 Strategic Diagnostics, Inc. Dispositif de dosage integre et ses procedes de production
US6979424B2 (en) 1998-03-17 2005-12-27 Cepheid Integrated sample analysis device
US7188001B2 (en) 1998-03-23 2007-03-06 Cepheid System and method for temperature control
EP1064360B1 (fr) 1998-03-27 2008-03-05 Prolume, Ltd. Luciferases, proteines fluorescentes gfp, leurs acides nucleiques, et leur utilisation en diagnostic
US6235534B1 (en) 1998-04-27 2001-05-22 Ronald Frederich Brookes Incremental absorbance scanning of liquid in dispensing tips
US6175752B1 (en) 1998-04-30 2001-01-16 Therasense, Inc. Analyte monitoring device and methods of use
ATE423622T1 (de) 1998-05-01 2009-03-15 Gen Probe Inc Automatisches isolierungs- und amplifizierungsverfahren für eine zielnukleinsäuresequenz
EP0955097B1 (fr) 1998-05-04 2004-10-06 F. Hoffmann-La Roche Ag Dispositif de cycles thermiques avec positionnement automatique du couvercle
US6200531B1 (en) 1998-05-11 2001-03-13 Igen International, Inc. Apparatus for carrying out electrochemiluminescence test measurements
US7394363B1 (en) 1998-05-12 2008-07-01 Bahador Ghahramani Intelligent multi purpose early warning system for shipping containers, components therefor and methods of making the same
US7498164B2 (en) 1998-05-16 2009-03-03 Applied Biosystems, Llc Instrument for monitoring nucleic acid sequence amplification reaction
US6287765B1 (en) 1998-05-20 2001-09-11 Molecular Machines, Inc. Methods for detecting and identifying single molecules
EP0962773A1 (fr) 1998-06-03 1999-12-08 Mark Howard Jones Procédés d'essai, dispositif et marqueurs à base d'électrochimie
JP3389106B2 (ja) 1998-06-11 2003-03-24 松下電器産業株式会社 電気化学分析素子
US6780617B2 (en) 2000-12-29 2004-08-24 Chen & Chen, Llc Sample processing device and method
US6743605B1 (en) 1998-06-24 2004-06-01 Enzo Life Sciences, Inc. Linear amplification of specific nucleic acid sequences
EP1192089A1 (fr) 1998-07-06 2002-04-03 The Coca-Cola Company Panier avec logement faconne dans sa structure
GB9816088D0 (en) 1998-07-23 1998-09-23 Axis Biochemicals Asa System
US6091490A (en) 1998-07-30 2000-07-18 The United States Of America As Represented By The Secretary Of The Navy Fiber-optic pipette (FOP) for rapid long pathlength capillary spectroscopy
DE19835833A1 (de) 1998-08-07 2000-02-17 Max Planck Gesellschaft Dosierkopf zur parallelen Bearbeitung einer Vielzahl von Fluidproben
US6562300B2 (en) 1998-08-28 2003-05-13 Becton, Dickinson And Company Collection assembly
US6132582A (en) * 1998-09-14 2000-10-17 The Perkin-Elmer Corporation Sample handling system for a multi-channel capillary electrophoresis device
US6517475B1 (en) 1998-09-25 2003-02-11 Baldwin Filters, Inc. Centrifugal filter for removing soot from engine oil
US6159368A (en) * 1998-10-29 2000-12-12 The Perkin-Elmer Corporation Multi-well microfiltration apparatus
ATE374833T1 (de) 1998-11-09 2007-10-15 Eiken Chemical Verfahren zur synthese von nukleinsäuren
US20100262432A1 (en) 1998-11-13 2010-10-14 Anuthep Benja-Athon Computer-created-consensus-based health-care system
US20030012699A1 (en) * 1998-11-18 2003-01-16 Thomas Moore Simultaneous handling of magnetic beads in a two-dimensional arrangement
US6309828B1 (en) 1998-11-18 2001-10-30 Agilent Technologies, Inc. Method and apparatus for fabricating replicate arrays of nucleic acid molecules
RU2147123C1 (ru) 1998-12-16 2000-03-27 Боев Сергей Федотович Способ анализа клеточного состава крови по мазку
US6887693B2 (en) 1998-12-24 2005-05-03 Cepheid Device and method for lysing cells, spores, or microorganisms
US7914994B2 (en) 1998-12-24 2011-03-29 Cepheid Method for separating an analyte from a sample
WO2000040749A2 (fr) 1999-01-06 2000-07-13 Genenews Inc. Technique de detection de transcrits geniques dans le sang et leur utilisation
US6197254B1 (en) 1999-01-11 2001-03-06 International Food Protection Self-contained assaying apparatus
EP1054250B1 (fr) * 1999-01-25 2002-09-04 Hamamatsu Photonics K.K. Adaptateur de pipette, pipette de mesure par absorbance, procede et appareil de mesure par absorbance
US7450229B2 (en) 1999-01-25 2008-11-11 Amnis Corporation Methods for analyzing inter-cellular phenomena
US8885913B2 (en) 1999-01-25 2014-11-11 Amnis Corporation Detection of circulating tumor cells using imaging flow cytometry
US8005314B2 (en) 2005-12-09 2011-08-23 Amnis Corporation Extended depth of field imaging for high speed object analysis
US6348176B1 (en) 1999-02-11 2002-02-19 Careside, Inc. Cartridge-based analytical instrument using centrifugal force/pressure for metering/transport of fluids
GB9903906D0 (en) 1999-02-19 1999-04-14 Microbiological Res Authority Method and apparatus for nucleic acid strand separation
US6215894B1 (en) 1999-02-26 2001-04-10 General Scanning, Incorporated Automatic imaging and analysis of microarray biochips
US8636648B2 (en) 1999-03-01 2014-01-28 West View Research, Llc Endoscopic smart probe
EP1173744A4 (fr) * 1999-03-02 2002-10-16 Qualigen Inc Procedes et appareil de separation de fluides biologiques
EP1127611A3 (fr) 1999-03-03 2001-11-07 Symyx Technologies, Inc. Microsystèmes de traitement chimique avec d' analyse intégrée basée sur la séparation des produits de réaction
JP3524419B2 (ja) 1999-03-08 2004-05-10 アロカ株式会社 吸光度測定装置
US20020176801A1 (en) 1999-03-23 2002-11-28 Giebeler Robert H. Fluid delivery and analysis systems
EP1041386B1 (fr) * 1999-03-25 2007-10-17 Tosoh Corporation Analyseur
US6305804B1 (en) 1999-03-25 2001-10-23 Fovioptics, Inc. Non-invasive measurement of blood component using retinal imaging
US6699669B2 (en) * 1999-04-09 2004-03-02 Space Hardware Optimization Technology, Inc. Multistage electromagnetic separator for purifying cells, chemicals and protein structures
US20050100943A1 (en) * 2000-04-11 2005-05-12 Hideki Kambara Method of producing probe arrays for biological materials using fine particles
US6143252A (en) 1999-04-12 2000-11-07 The Perkin-Elmer Corporation Pipetting device with pipette tip for solid phase reactions
US20020177135A1 (en) 1999-07-27 2002-11-28 Doung Hau H. Devices and methods for biochip multiplexing
US20040053290A1 (en) 2000-01-11 2004-03-18 Terbrueggen Robert Henry Devices and methods for biochip multiplexing
JP4085514B2 (ja) 1999-04-30 2008-05-14 株式会社島津製作所 電気泳動チップ
JP2003523940A (ja) 1999-05-11 2003-08-12 オーソ−マクネイル ファーマシューティカル インコーポレイテッド エリスロポエチン投与の薬物速度論的および薬力学的モデリング
US6582964B1 (en) 1999-05-12 2003-06-24 Cme Telemetrix Inc. Method and apparatus for rapid measurement of HbA1c
US6716396B1 (en) 1999-05-14 2004-04-06 Gen-Probe Incorporated Penetrable cap
US7056661B2 (en) 1999-05-19 2006-06-06 Cornell Research Foundation, Inc. Method for sequencing nucleic acid molecules
US6544732B1 (en) 1999-05-20 2003-04-08 Illumina, Inc. Encoding and decoding of array sensors utilizing nanocrystals
US6818185B1 (en) 1999-05-28 2004-11-16 Cepheid Cartridge for conducting a chemical reaction
DE60022025T2 (de) 1999-05-28 2006-06-29 Cepheid, Sunnyvale Anlage zum brechen von zellen
US7068361B2 (en) 1999-06-03 2006-06-27 Baxter International Apparatus, systems and methods for processing and treating a biological fluid with light
US6056661A (en) 1999-06-14 2000-05-02 General Motors Corporation Multi-range transmission with input split planetary gear set and continuously variable transmission unit
WO2000078454A1 (fr) 1999-06-22 2000-12-28 Agilent Technologies, Inc. Appareil de commande d'un dispositif microfluidique
US7195670B2 (en) 2000-06-27 2007-03-27 California Institute Of Technology High throughput screening of crystallization of materials
US7951612B2 (en) * 1999-07-08 2011-05-31 Lee H. Angros In situ heat induced antigen recovery and staining apparatus and method
EP1196757B1 (fr) 1999-07-09 2004-01-07 Genevac Limited Evaporateur centrifuge pour echantillons a ecran de protection contre la chaleur directe et chauffage uniforme
US20020010145A1 (en) * 1999-07-12 2002-01-24 Willson Richard C. Apparatus, methods and compositions for biotechnical separations
US6353475B1 (en) 1999-07-12 2002-03-05 Caliper Technologies Corp. Light source power modulation for use with chemical and biochemical analysis
US7138254B2 (en) * 1999-08-02 2006-11-21 Ge Healthcare (Sv) Corp. Methods and apparatus for performing submicroliter reactions with nucleic acids or proteins
US6423536B1 (en) * 1999-08-02 2002-07-23 Molecular Dynamics, Inc. Low volume chemical and biochemical reaction system
US6244119B1 (en) 1999-08-03 2001-06-12 Wallac Oy Multichannel pipette system and pipette tips therefor
AU6524100A (en) 1999-08-06 2001-03-05 Thermo Biostar Inc. An automated point of care detection system including complete sample processingcapabilities
TW517154B (en) 1999-08-11 2003-01-11 Asahi Chemical Ind Analyzing cartridge and liquid feed control device
JP2001065458A (ja) 1999-08-25 2001-03-16 Matsushita Electric Ind Co Ltd 圧縮機
US6858185B1 (en) 1999-08-25 2005-02-22 Caliper Life Sciences, Inc. Dilutions in high throughput systems with a single vacuum source
RU2148438C1 (ru) 1999-08-31 2000-05-10 Корчагин Александр Васильевич Центрифуга
CN1192567C (zh) 1999-09-09 2005-03-09 诺基亚公司 基于功率频谱密度估计的数据速率确定
US20030175993A1 (en) * 1999-09-10 2003-09-18 Anthony Toranto Ketone assay
DK1431303T3 (en) 1999-09-13 2014-02-17 Nugen Technologies Inc A composition for isothermal linear amplification of polynucleotide sequences
DE19944516B4 (de) 1999-09-16 2006-08-17 Brainlab Ag Dreidimensionale Formerfassung mit Kamerabildern
US6835184B1 (en) 1999-09-24 2004-12-28 Becton, Dickinson And Company Method and device for abrading skin
US6675037B1 (en) 1999-09-29 2004-01-06 Regents Of The University Of Minnesota MRI-guided interventional mammary procedures
WO2001023610A2 (fr) 1999-09-29 2001-04-05 Solexa Ltd. Sequençage de polynucleotides
US6368275B1 (en) 1999-10-07 2002-04-09 Acuson Corporation Method and apparatus for diagnostic medical information gathering, hyperthermia treatment, or directed gene therapy
JP3481578B2 (ja) 1999-10-12 2003-12-22 松下電器産業株式会社 電子放出素子およびそれを利用した電子源、電界放出型画像表示装置、蛍光灯、並びにそれらの製造方法
US7329388B2 (en) * 1999-11-08 2008-02-12 Princeton Biochemicals, Inc. Electrophoresis apparatus having staggered passage configuration
US6471916B1 (en) 1999-11-09 2002-10-29 Packard Instrument Company Apparatus and method for calibration of a microarray scanning system
US6361958B1 (en) 1999-11-12 2002-03-26 Motorola, Inc. Biochannel assay for hybridization with biomaterial
US6750053B1 (en) 1999-11-15 2004-06-15 I-Stat Corporation Apparatus and method for assaying coagulation in fluid samples
US6491666B1 (en) 1999-11-17 2002-12-10 Microchips, Inc. Microfabricated devices for the delivery of molecules into a carrier fluid
JP3441058B2 (ja) 1999-12-03 2003-08-25 理化学研究所 キャピラリーゲル電気泳動用マイクロチップおよびその製造方法
JP2001165752A (ja) 1999-12-06 2001-06-22 Hitachi Ltd 血清量測定装置および測定方法
GB9930000D0 (en) 1999-12-21 2000-02-09 Phaeton Research Ltd An ingestible device
JP4497335B2 (ja) 1999-12-22 2010-07-07 ベックマン・コールター・インコーポレーテッド 分析装置
US7747312B2 (en) 2000-01-04 2010-06-29 George Mason Intellectual Properties, Inc. System and method for automatic shape registration and instrument tracking
ATE350160T1 (de) 2000-01-11 2007-01-15 Clinical Micro Sensors Inc Patrone, die einen biochip enthält
US6361486B1 (en) 2000-02-29 2002-03-26 Agilent Technologies, Inc. Coaxial-drive centrifuge providing tilt control relative to centrifugal force
WO2001064344A2 (fr) 2000-03-02 2001-09-07 Microchips, Inc. Dispositifs microfabriques destines au stockage et a l'exposition selective de produits chimiques et de dispositifs
CN1255676C (zh) 2000-03-09 2006-05-10 医疗分析公司 医疗诊断系统
BR0109159A (pt) 2000-03-15 2004-09-28 Emedicalfiles Inc Sistema de gerenciamento de informações, médicas e de, saúde, hospedado na web
DE10013511A1 (de) 2000-03-20 2001-10-11 Brand Gmbh & Co Kg Mehrkanal-Pipettiereinrichtung sowie Pipettenschaft dafür
US6488827B1 (en) * 2000-03-31 2002-12-03 Lifescan, Inc. Capillary flow control in a medical diagnostic device
US6413213B1 (en) 2000-04-18 2002-07-02 Roche Diagnostics Corporation Subscription based monitoring system and method
ATE420189T1 (de) 2000-04-28 2009-01-15 St Jude Childrens Res Hospital Dna-transfektionssystem zur erzeugung von infektiösen negativsträngigen rna virus
DE10022693C1 (de) 2000-05-05 2001-10-11 Cybio Instr Gmbh Pipettierautomat mit einem Einreihigen-Mehrkanal-Pipettierkopf
US20020052761A1 (en) 2000-05-11 2002-05-02 Fey Christopher T. Method and system for genetic screening data collection, analysis, report generation and access
JP2003533682A (ja) 2000-05-15 2003-11-11 テカン・トレーディング・アクチェンゲゼルシャフト 双方向流動遠心ミクロ流体装置
US7006858B2 (en) 2000-05-15 2006-02-28 Silver James H Implantable, retrievable sensors and immunosensors
US6917726B2 (en) 2001-09-27 2005-07-12 Cornell Research Foundation, Inc. Zero-mode clad waveguides for performing spectroscopy with confined effective observation volumes
US6943035B1 (en) 2000-05-19 2005-09-13 Genetix Limited Liquid dispensing apparatus and method
IL163684A0 (en) 2000-05-31 2005-12-18 Given Imaging Ltd Measurement of electrical characteristics of tissue
AU2001265012B2 (en) 2000-06-01 2006-07-13 Georgetown University Systems and methods for monitoring health and delivering drugs transdermally
US8071051B2 (en) 2004-05-14 2011-12-06 Honeywell International Inc. Portable sample analyzer cartridge
WO2001093743A2 (fr) 2000-06-07 2001-12-13 Healthetech, Inc. Analyseur d'haleine pour detecter la presence de cetones
US7276158B1 (en) 2000-06-09 2007-10-02 Ashok K Shukla Incision-based filtration/separation pipette tip
JP3638503B2 (ja) * 2000-06-12 2005-04-13 アークレイ株式会社 カートリッジ式容器を用いる測定装置および測定方法並びに記録媒体
US6465953B1 (en) 2000-06-12 2002-10-15 General Electric Company Plastic substrates with improved barrier properties for devices sensitive to water and/or oxygen, such as organic electroluminescent devices
FR2810407B1 (fr) 2000-06-16 2002-08-02 Philippe Escal Appareil pour l'analyse d'echantillons
CA2415319A1 (fr) * 2000-06-16 2001-12-20 Martek Biosciences Corporation Phycobiliproteine de recombinaison, proteines de fusion a liaison par phycobiliproteine et utilisations a cet effet
US6859830B1 (en) 2000-06-23 2005-02-22 Microsoft Corporation Method and system for detecting a dead server
US6468474B2 (en) 2000-07-06 2002-10-22 Varian, Inc. Saliva testing and confirmation device
US6603987B2 (en) 2000-07-11 2003-08-05 Bayer Corporation Hollow microneedle patch
US6806604B2 (en) 2000-07-13 2004-10-19 Kendro Laboratory Products Gmbh Centrifuge with a magnetically stabilized rotor for centrifugal goods
JP2002031055A (ja) 2000-07-14 2002-01-31 Matsushita Electric Ind Co Ltd 密閉型圧縮機
WO2002007064A2 (fr) 2000-07-17 2002-01-24 Labnetics, Inc. Procede et appareil pour le traitement des informations electroniques collectees a distance caracterisant les proprietes d'entites biologiques
EP1304959A1 (fr) 2000-07-24 2003-05-02 Motorola, Inc. Capsule electronique a ingerer
JP2002044007A (ja) 2000-07-26 2002-02-08 Ricoh Elemex Corp 携帯電話機
US20040005582A1 (en) 2000-08-10 2004-01-08 Nanobiodynamics, Incorporated Biospecific desorption microflow systems and methods for studying biospecific interactions and their modulators
US6905886B2 (en) 2000-08-11 2005-06-14 Quest Diagnostics Investments Incorporated Preservative solutions
US6797518B1 (en) 2000-09-11 2004-09-28 Ortho-Clinical Diagnostics, Inc. Analysis method with sample quality measurement
DE10046110B8 (de) 2000-09-18 2006-07-06 Siemens Ag Medizinisches Diagnosegerät mit Patientenerkennung
WO2002026286A2 (fr) 2000-09-27 2002-04-04 Cobe Cardiovascular, Inc. Systeme de perfusion sanguine
US6689615B1 (en) * 2000-10-04 2004-02-10 James Murto Methods and devices for processing blood samples
WO2002031747A1 (fr) 2000-10-13 2002-04-18 Irm Llc Systeme de traitement a haut rendement et procede d'utilisation
CA2360194C (fr) 2000-10-25 2008-10-07 Micronix, Inc. Microcuvette pour l'analyse de corps a l'etat solide utilisant des pellicules seches
US20020139936A1 (en) 2000-10-27 2002-10-03 Dumas David P. Apparatus for fluorescence detection on arrays
EP1332000B1 (fr) 2000-10-30 2012-06-20 Sequenom, Inc. Procede d'apport de volumes inferieurs au microlitre sur un substrat
US6929636B1 (en) 2000-11-08 2005-08-16 Hewlett-Packard Development Company, L.P. Internal drug dispenser capsule medical device
AU2001295361A1 (en) 2000-11-17 2002-05-27 Tecan Trading Ag Method and device for determining the volume of a sample of a liquid
US6905816B2 (en) * 2000-11-27 2005-06-14 Intelligent Medical Devices, Inc. Clinically intelligent diagnostic devices and methods
JP2002161856A (ja) 2000-11-28 2002-06-07 Matsushita Electric Ind Co Ltd シャフトおよびシャフトの製造方法
JP2004537713A (ja) 2000-12-01 2004-12-16 セテク コーポレイション 高処理量の毛管電気泳動システム
EP1363736B1 (fr) 2000-12-18 2011-03-02 Protedyne Corporation Extrusion du gel pour electrophorese sur gel
GB0030929D0 (en) 2000-12-19 2001-01-31 Inverness Medical Ltd Analyte measurement
US6312929B1 (en) 2000-12-22 2001-11-06 Cepheid Compositions and methods enabling a totally internally controlled amplification reaction
AU2002243360A1 (en) 2000-12-26 2002-08-06 C. Frederick Battrell Microfluidic cartridge with integrated electronics
JP2003144176A (ja) 2000-12-27 2003-05-20 Inst Of Physical & Chemical Res 遺伝子多型の検出方法
US6870797B2 (en) 2001-01-04 2005-03-22 Hewlett-Packard Development Company, L.P. Media storage system using a transponder for transmitting data signal
US7435384B2 (en) 2001-01-08 2008-10-14 Leonard Fish Diagnostic instrument with movable electrode mounting member and methods for detecting analytes
US7205157B2 (en) 2001-01-08 2007-04-17 Becton, Dickinson And Company Method of separating cells from a sample
CA2366802A1 (fr) 2001-01-17 2002-07-17 Bayer Corporation Methode et appareil permettant d'utiliser les releves infrarouges pour detecter les erreurs d'identification d'une bande d'essai diagnostique utilisee dans un spectrometre a reflectance
US7315784B2 (en) 2001-02-15 2008-01-01 Siemens Aktiengesellschaft Network for evaluating data obtained in a biochip measurement device
US6484104B2 (en) 2001-02-15 2002-11-19 Klaus Abraham-Fuchs Network for evaluating data obtained in a biochip measurement device
US7567913B2 (en) 2001-02-16 2009-07-28 Quest Diagnostics Inc. Method and system for ordering a laboratory test for a patient and obtaining results thereof
US6612985B2 (en) 2001-02-26 2003-09-02 University Of Rochester Method and system for monitoring and treating a patient
US6899848B1 (en) 2001-02-27 2005-05-31 Hamilton Company Automated sample treatment system: apparatus and method
US6341490B1 (en) * 2001-03-03 2002-01-29 Gilson, Inc. Heat transfer apparatus for sample containing well plates
US6949377B2 (en) 2001-03-05 2005-09-27 Ho Winston Z Chemiluminescence-based microfluidic biochip
JP2002266762A (ja) 2001-03-07 2002-09-18 Matsushita Electric Ind Co Ltd 冷凍サイクル装置
KR20030082535A (ko) 2001-03-09 2003-10-22 뉴젠 테크놀로지스 인코포레이티드 Ｒｎａ 서열의 증폭을 위한 방법 및 조성물
US6893612B2 (en) 2001-03-09 2005-05-17 Gen-Probe Incorporated Penetrable cap
JP2002263185A (ja) 2001-03-12 2002-09-17 Sanyo Electric Co Ltd 投薬システム及び方法及び投薬装置
US6748337B2 (en) 2001-03-14 2004-06-08 Wardlaw Partners, Lp Method and apparatus for providing quality control in an instrument for medical analysis
JP2002282217A (ja) 2001-03-27 2002-10-02 Sysmex Corp 測定装置及びそれを含む測定結果管理システム
US7010391B2 (en) 2001-03-28 2006-03-07 Handylab, Inc. Methods and systems for control of microfluidic devices
US20040044560A1 (en) 2001-04-05 2004-03-04 Joe Giglio Kiosk with body fat analyzer
US7458483B2 (en) 2001-04-24 2008-12-02 Abbott Laboratories, Inc. Assay testing diagnostic analyzer
WO2002089972A1 (fr) * 2001-05-03 2002-11-14 Commissariat A L'energie Atomique Dispositif microfluidique destine a l'analyse d'acides nucleiques et/ou de proteines, ses procedes de preparation et son utilisation
EP1387671A1 (fr) 2001-05-03 2004-02-11 MASSACHUSETTS EYE & EAR INFIRMARY Dispositif d'administration de medicament implantable et utilisation associee
US20030211618A1 (en) 2001-05-07 2003-11-13 Patel Gordhandhai Nathalal Color changing steam sterilization indicator
EP1390760B1 (fr) 2001-05-09 2008-06-18 Axis-Shield Asa Systeme de dosage
US6591124B2 (en) 2001-05-11 2003-07-08 The Procter & Gamble Company Portable interstitial fluid monitoring system
US20050009101A1 (en) 2001-05-17 2005-01-13 Motorola, Inc. Microfluidic devices comprising biochannels
US6919046B2 (en) 2001-06-07 2005-07-19 Nanostream, Inc. Microfluidic analytical devices and methods
JP2002371955A (ja) 2001-06-15 2002-12-26 Sanuki Kogyo Kk 往復駆動装置及び該装置を使用した送液ポンプ
EP1270078B1 (fr) 2001-06-22 2004-09-15 Jouan Italia S.R.L. Appareil et procédé pour charger et décharger, automatiquement de godets pour centrifugeuse
AUPR604101A0 (en) 2001-06-29 2001-07-26 Unisearch Limited Aptamers
CA2764307C (fr) 2001-06-29 2015-03-03 Meso Scale Technologies, Llc. Plaques d'epreuve, systemes lecteurs et methodes de mesures de tests par luminescence
US20030208113A1 (en) 2001-07-18 2003-11-06 Mault James R Closed loop glycemic index system
US6833441B2 (en) 2001-08-01 2004-12-21 Abmaxis, Inc. Compositions and methods for generating chimeric heteromultimers
JP3775263B2 (ja) 2001-08-10 2006-05-17 ニプロ株式会社 記録媒体およびこの記録媒体を用いた血糖測定システム
WO2003014741A1 (fr) 2001-08-10 2003-02-20 Matsushita Electric Industrial Co., Ltd. Biodetecteur et procede servant a analyser des constituants sanguins au moyen de ce dernier
AU2002330756B2 (en) * 2001-08-10 2009-07-16 Ahram Biosystems Inc. System for detecting protease
US20030095897A1 (en) * 2001-08-31 2003-05-22 Grate Jay W. Flow-controlled magnetic particle manipulation
US6751491B2 (en) 2001-09-01 2004-06-15 M Biotech Inc Analyte measuring biosensor chip using image scanning system
US8024395B1 (en) 2001-09-04 2011-09-20 Gary Odom Distributed processing multiple tier task allocation
US20030139886A1 (en) 2001-09-05 2003-07-24 Bodzin Leon J. Method and apparatus for normalization and deconvolution of assay data
JP2005518553A (ja) * 2001-09-06 2005-06-23 ジェノミック プロファイリング システムズ インコーポレイティッド 細胞およびウイルスの迅速かつ高感度な検出方法
US20030052074A1 (en) 2001-09-17 2003-03-20 Chang Min Shuan Closure for container for holding biological samples
US7854896B2 (en) 2001-09-25 2010-12-21 Becton, Dickinson And Company Closed system storage plates
JP4754746B2 (ja) * 2001-09-28 2011-08-24 オリンパス株式会社 棒状担体およびこれを具備するシリンダー反応容器
US6805842B1 (en) 2001-10-12 2004-10-19 Mds Sciex Repuncturable self-sealing sample container with internal collapsible bag
US6966880B2 (en) 2001-10-16 2005-11-22 Agilent Technologies, Inc. Universal diagnostic platform
US20060121502A1 (en) 2001-11-09 2006-06-08 Robert Cain Microfluidics apparatus for cantilevers and methods of use therefor
US7794994B2 (en) * 2001-11-09 2010-09-14 Kemeta, Llc Enzyme-based system and sensor for measuring acetone
JP2003222611A (ja) 2001-11-20 2003-08-08 Nec Corp 分離装置、分離方法および分離装置の製造方法
US7635588B2 (en) 2001-11-29 2009-12-22 Applied Biosystems, Llc Apparatus and method for differentiating multiple fluorescence signals by excitation wavelength
JP2003166910A (ja) 2001-11-30 2003-06-13 Asahi Kasei Corp 送液機構及び該送液機構を備える分析装置
JP2003167960A (ja) 2001-12-04 2003-06-13 Ikuo Kondo 健康管理システム
US20030157723A1 (en) 2001-12-04 2003-08-21 Dave Smith Immunoassay chemistry cassette barcode for system customization
US20050027182A1 (en) 2001-12-27 2005-02-03 Uzair Siddiqui System for monitoring physiological characteristics
US6583879B1 (en) 2002-01-11 2003-06-24 X-Rite, Incorporated Benchtop spectrophotometer with improved targeting
JP2003207454A (ja) 2002-01-15 2003-07-25 Minolta Co Ltd 透過光検出装置
US7133547B2 (en) 2002-01-24 2006-11-07 Tripath Imaging, Inc. Method for quantitative video-microscopy and associated system and computer software program product
WO2003065030A1 (fr) * 2002-01-25 2003-08-07 Irm, Llc Systemes et procedes de gestion de fluides
FI112093B (fi) 2002-01-30 2003-10-31 Boreal Plant Breeding Ltd Menetelmä ja testipakkaus geneettisen identiteetin osoittamiseksi
US20040109793A1 (en) 2002-02-07 2004-06-10 Mcneely Michael R Three-dimensional microfluidics incorporating passive fluid control structures
US7004928B2 (en) 2002-02-08 2006-02-28 Rosedale Medical, Inc. Autonomous, ambulatory analyte monitor or drug delivery device
US20030212379A1 (en) 2002-02-26 2003-11-13 Bylund Adam David Systems and methods for remotely controlling medication infusion and analyte monitoring
US20040174821A1 (en) * 2003-03-04 2004-09-09 Christian Eggeling Method for detecting the impacts of interfering effects on experimental data
CA2419200C (fr) 2002-03-05 2015-06-30 Bayer Healthcare Llc Appareil de prelevement de fluide muni d'une lancette integree et d'une zone de reaction
JP2003315348A (ja) 2002-04-22 2003-11-06 Hitachi High-Technologies Corp 検体処理システム及びそれを用いた検体検査自動化システム
EP1498067A1 (fr) 2002-04-25 2005-01-19 Matsushita Electric Industrial Co., Ltd. Dispositif de determination de dose, injecteur et systeme de gestion sanitaire
JP2003322653A (ja) 2002-05-07 2003-11-14 Toshiba Corp プローブ固定支持体及びプローブ固定担体
US20030143113A2 (en) 2002-05-09 2003-07-31 Lifescan, Inc. Physiological sample collection devices and methods of using the same
JP3839349B2 (ja) 2002-05-15 2006-11-01 株式会社堀場製作所 化学発光酵素免疫測定装置
WO2003097808A2 (fr) 2002-05-17 2003-11-27 Becton, Dickinson And Company Systeme automatise destine a isoler, amplifier et detecter une sequence d'acides nucleiques cibles
US7055368B2 (en) 2002-05-21 2006-06-06 Kendro Laboratory Products, Inc. Automatic calibration of an imbalance detector
US7151167B2 (en) * 2002-06-10 2006-12-19 Phynexus, Inc. Open channel solid phase extraction systems and methods
AU2003232168A1 (en) 2002-06-11 2003-12-22 Chempaq A/S Lysing reagent, cartridge and automatic electronic cell counter for simultaneous enumeration of different types of white blood cells
US7272252B2 (en) 2002-06-12 2007-09-18 Clarient, Inc. Automated system for combining bright field and fluorescent microscopy
FR2841249A1 (fr) 2002-06-19 2003-12-26 Genfit S A Compositions et methodes pour le dosage de l'apo b48 et de l'apo b100
JP4106977B2 (ja) 2002-06-21 2008-06-25 株式会社日立製作所 分析チップ及び分析装置
US6730510B2 (en) 2002-07-02 2004-05-04 Organogenesis, Inc. Culture dish and bioreactor system
DK1539352T3 (da) 2002-07-23 2010-04-19 Protedyne Corp Væskehåndteringsværktøj, der har hult stempel
FR2842912B1 (fr) 2002-07-25 2004-09-10 Junior Instruments Procede et dispositf pour le pretraitement par centrifugeage d'echantillons.
JP2004069395A (ja) * 2002-08-02 2004-03-04 Nec Corp マイクロチップ、マイクロチップの製造方法および成分検出方法
US20040029266A1 (en) 2002-08-09 2004-02-12 Emilio Barbera-Guillem Cell and tissue culture device
US8200438B2 (en) 2002-08-19 2012-06-12 Escreen, Inc. Method and computer program for creating electronic custody and control forms for human assay test samples
US6780645B2 (en) 2002-08-21 2004-08-24 Lifescan, Inc. Diagnostic kit with a memory storing test strip calibration codes and related methods
CN2559986Y (zh) 2002-08-23 2003-07-09 上海博昇微晶科技有限公司 集成微流体和微阵列探针的微芯片
US20040038385A1 (en) 2002-08-26 2004-02-26 Langlois Richard G. System for autonomous monitoring of bioagents
US7188731B2 (en) 2002-08-26 2007-03-13 The Regents Of The University Of California Variable flexure-based fluid filter
US20070166725A1 (en) 2006-01-18 2007-07-19 The Regents Of The University Of California Multiplexed diagnostic platform for point-of care pathogen detection
JP2004101381A (ja) 2002-09-10 2004-04-02 Nittec Co Ltd 自動分析装置用の複光路セル及びこの複光路セルを用いた分析方法
CA2498764C (fr) 2002-09-20 2015-11-10 New England Biolabs, Inc. Amplification dependant de l'helicase des acides nucleiques
US7397601B2 (en) 2004-11-24 2008-07-08 Laudo John S Optical system for cell imaging
US7177767B2 (en) 2002-10-18 2007-02-13 Abaxis, Inc. Systems and methods for the detection of short and long samples
US20040086872A1 (en) 2002-10-31 2004-05-06 Childers Winthrop D. Microfluidic system for analysis of nucleic acids
US7390457B2 (en) 2002-10-31 2008-06-24 Agilent Technologies, Inc. Integrated microfluidic array device
JP2006505283A (ja) 2002-11-08 2006-02-16 フアルマシア・コーポレーシヨン 高速処理自動化核酸単離及び定量法
US6915919B2 (en) 2002-11-21 2005-07-12 American Bio Medica Corporation Container closure cap with self-sealing slot
JP3799323B2 (ja) 2002-11-29 2006-07-19 Ｎｅｃインフロンティア株式会社 情報端末装置及びｐｃカード
AU2003296946A1 (en) 2002-12-12 2004-07-09 Chiron Corporation A biological sample storage device and method for biological sample contamination testing
CN1173182C (zh) 2002-12-18 2004-10-27 陕西超英生物医学研究开发有限公司 糖尿病自身免疫抗体检测蛋白芯片、其制备及检测方法
US20060094108A1 (en) 2002-12-20 2006-05-04 Karl Yoder Thermal cycler for microfluidic array assays
US7110107B2 (en) 2002-12-20 2006-09-19 Corning Incorporated Capillary assay device and method
US20040120848A1 (en) 2002-12-20 2004-06-24 Maria Teodorczyk Method for manufacturing a sterilized and calibrated biosensor-based medical device
US7648678B2 (en) 2002-12-20 2010-01-19 Dako Denmark A/S Method and system for pretreatment of tissue slides
WO2004061418A2 (fr) * 2002-12-26 2004-07-22 Meso Scale Technologies, Llc. Cartouches d'essai et procedes d'utilisation
US20040129676A1 (en) * 2003-01-07 2004-07-08 Tan Roy H. Apparatus for transfer of an array of liquids and methods for manufacturing same
DE10307030A1 (de) 2003-02-20 2004-09-09 Eppendorf Ag Dosiersystem
GB0303913D0 (en) 2003-02-21 2003-03-26 Sophion Bioscience As Robot centrifugation device
DE10312197A1 (de) 2003-03-19 2004-09-30 Roche Diagnostics Gmbh Probenbehandlungsgerät, insbesondere automatisches Analysegerät
JP4464172B2 (ja) 2003-03-31 2010-05-19 キヤノン株式会社 生化学反応カートリッジ及びその使用方法
WO2004087322A2 (fr) 2003-04-04 2004-10-14 Koninklijke Philips Electronics N.V. Separation de fluides dans des microcanaux multiples
US20050010098A1 (en) 2003-04-11 2005-01-13 Sigmund Frigstad Method and apparatus for knowledge based diagnostic imaging
JP4260541B2 (ja) 2003-05-12 2009-04-30 旭化成ファーマ株式会社 糖化タンパク質測定用試験片
US20040230400A1 (en) 2003-05-13 2004-11-18 Tomasso David Angelo Analyzer having concentric rotors
US20040228766A1 (en) 2003-05-14 2004-11-18 Witty Thomas R. Point of care diagnostic platform
AU2003902422A0 (en) 2003-05-19 2003-06-05 Intellirad Solutions Pty. Ltd Access security system
US7185551B2 (en) 2003-05-22 2007-03-06 Schwartz H Donald Pipetting module
JP2004348496A (ja) 2003-05-23 2004-12-09 Hitachi Ltd 通信システム
US20040241048A1 (en) 2003-05-30 2004-12-02 Applera Corporation Thermal cycling apparatus and method for providing thermal uniformity
EP1629285A2 (fr) 2003-06-05 2006-03-01 Bioprocessors Corporation Systeme et procede destines a une automatisation
US7258673B2 (en) 2003-06-06 2007-08-21 Lifescan, Inc Devices, systems and methods for extracting bodily fluid and monitoring an analyte therein
EP1635700B1 (fr) * 2003-06-13 2016-03-09 Sanofi-Aventis Deutschland GmbH Appareil pour dispositif d'analyse sur le lieu de soin
US7702524B1 (en) 2003-06-16 2010-04-20 Scheduling.Com, Inc. Method and system for online secure patient referral system
KR20060024808A (ko) 2003-06-20 2006-03-17 유니바사루 바이오 리사치 가부시키가이샤 시료배열ㆍ집적화 장치, 그 방법, 및 시료 집적체 사용장치
JP3918178B2 (ja) 2003-06-23 2007-05-23 大阪瓦斯株式会社 高純度ナノスケールカーボンチューブ含有炭素質材料の製造法
US7824623B2 (en) 2003-06-24 2010-11-02 Millipore Corporation Multifunctional vacuum manifold
CN1849064A (zh) * 2003-07-07 2006-10-18 先锋高级育种国际公司 Qtl“随时定位”方法
US20050009191A1 (en) 2003-07-08 2005-01-13 Swenson Kirk D. Point of care information management system
CN1849514A (zh) * 2003-07-08 2006-10-18 因韦尔尼斯医药瑞士股份有限公司 颗粒凝集的检测方法和装置
JP2005030983A (ja) 2003-07-09 2005-02-03 Matsushita Electric Ind Co Ltd 測定装置
JP4087302B2 (ja) 2003-07-10 2008-05-21 日本電子株式会社 検査装置
US7860727B2 (en) 2003-07-17 2010-12-28 Ventana Medical Systems, Inc. Laboratory instrumentation information management and control network
EP1650570B1 (fr) 2003-07-17 2021-05-26 LSI Medience Corporation Appareil à utiliser pour mesurer un composant contenu dans un échantillon comprenant un dispositif de mesure et une cartouche
US7381370B2 (en) 2003-07-18 2008-06-03 Dade Behring Inc. Automated multi-detector analyzer
US8346482B2 (en) 2003-08-22 2013-01-01 Fernandez Dennis S Integrated biosensor and simulation system for diagnosis and therapy
JP3888342B2 (ja) 2003-08-29 2007-02-28 ブラザー工業株式会社 ネットワーク装置
WO2005084534A1 (fr) 2003-09-03 2005-09-15 Life Patch International, Inc. Dispositifs de diagnostic personnel et procedes correspondants
JPWO2005024437A1 (ja) 2003-09-05 2007-11-08 日本電気株式会社 測定システム
EP2489434B1 (fr) 2003-09-09 2016-04-27 BioGenex Laboratories Système de traitement d'échantillons
US20050074873A1 (en) 2003-09-09 2005-04-07 Shanler Michael S. Tissue culture vessel
US7682833B2 (en) 2003-09-10 2010-03-23 Abbott Point Of Care Inc. Immunoassay device with improved sample closure
CA2896407A1 (fr) 2003-09-11 2005-03-24 Theranos, Inc. Dispositif medical permettant de surveiller un analyte et de distribuer des medicaments
US20060115384A1 (en) * 2003-09-16 2006-06-01 Vici Gig Harbor Group, Inc. Pipette tip surface sorption extraction
US7570443B2 (en) 2003-09-19 2009-08-04 Applied Biosystems, Llc Optical camera alignment
US20050225751A1 (en) 2003-09-19 2005-10-13 Donald Sandell Two-piece high density plate
DE10344700A1 (de) 2003-09-26 2005-04-14 Hirschmann Laborgeräte GmbH & Co. KG Mehrkanal-Pipettiervorrichtung
JP2005104750A (ja) 2003-09-29 2005-04-21 Matsushita Electric Ind Co Ltd ナノチューブの精製方法
JP4441618B2 (ja) 2003-10-06 2010-03-31 独立行政法人産業技術総合研究所 インフルエンザウイルスの検出方法
JP5021309B2 (ja) 2003-10-16 2012-09-05 ステファン ジョン ラルフ 免疫調節性組成物およびその使用方法
EP1678509B1 (fr) 2003-10-28 2008-04-16 DIESSE DIAGNOSTICA SENESE S.p.A. Dispositif pour la conduite d'analyses sur des fluides biologiques, et procede connexe
JP4073023B2 (ja) 2003-11-07 2008-04-09 財団法人新産業創造研究機構 微小流路デバイスおよびその作製方法
WO2005051197A2 (fr) 2003-11-26 2005-06-09 Koninklijke Philips Electronics, N.V. Optimisation du deroulement des operations pour un environnement d'imagerie a haut debit
WO2005121780A2 (fr) * 2003-12-09 2005-12-22 Board Of Regents, The University Of Texas System Procedes et appareil permettant de caracteriser, de mesurer et de distribuer des liquides
JP2007516446A (ja) * 2003-12-23 2007-06-21 ファストラック インコーポレイテッド ポイントオブケア診断プラットフォーム
JP4646809B2 (ja) 2003-12-26 2011-03-09 パナソニック株式会社 生体サンプル判別装置、生体サンプル判別方法、及び生体サンプル判別用プレート
JP4057539B2 (ja) 2004-01-09 2008-03-05 浜松ホトニクス株式会社 シースフローセルキュベット及びその製造方法
US7150995B2 (en) 2004-01-16 2006-12-19 Metrika, Inc. Methods and systems for point of care bodily fluid analysis
PT2611042E (pt) 2004-01-27 2015-04-13 Altivera L L C Tira de teste de imunoensaio integrando etiquetas de identificação por radiofrequência (rfid)
US20050164204A1 (en) * 2004-01-27 2005-07-28 Reed Thomas D. Single use lyophilized rnase reagents, and kits and methods for using same
US20050177057A1 (en) 2004-02-05 2005-08-11 Mitchell Friedman Automated breath collection device
US20050227370A1 (en) 2004-03-08 2005-10-13 Ramel Urs A Body fluid analyte meter & cartridge system for performing combined general chemical and specific binding assays
JP2005291954A (ja) * 2004-03-31 2005-10-20 Olympus Corp 使い捨て試薬パックとその試薬パックを用いる分析装置
DE602004014898D1 (de) * 2004-03-31 2008-08-21 Roche Diagnostics Gmbh Modulare Analysevorrichtung
EP1743161A2 (fr) 2004-04-06 2007-01-17 Bio/Data Corporation Dispositif d'essai jetable a fonction de mesure de volume d'echantillon et procedes de melange
US20080166753A1 (en) 2004-04-12 2008-07-10 University Technologies International Inc. Microbial Growth Assay
US20050236317A1 (en) * 2004-04-23 2005-10-27 Millipore Corporation Pendant drop control in a multiwell plate
US7887750B2 (en) 2004-05-05 2011-02-15 Bayer Healthcare Llc Analytical systems, devices, and cartridges therefor
CA2566538C (fr) 2004-05-13 2023-03-14 Anita Goel Amplification par la polymerase a l'echelle nanometrique: procedes et dispositifs pour l'amplification et la detection d'acides nucleiques
FR2871150B1 (fr) 2004-06-04 2006-09-22 Univ Lille Sciences Tech Dispositif de manipulation de gouttes destine a l'analyse biochimique, procede de fabrication du dispositif, et systeme d'analyse microfluidique
US8211386B2 (en) * 2004-06-08 2012-07-03 Biokit, S.A. Tapered cuvette and method of collecting magnetic particles
TWI547431B (zh) 2004-06-09 2016-09-01 史密斯克萊美占公司 生產藥物之裝置及方法
US8187535B2 (en) 2004-06-14 2012-05-29 Parker-Hannifin Corporation Robotic handling system and method with independently operable detachable tools
US20060057559A1 (en) 2004-06-23 2006-03-16 Rigel Pharmaceuticals, Inc. High-throughput cell migration screening assay
JP4416579B2 (ja) 2004-06-23 2010-02-17 株式会社日立ハイテクノロジーズ 自動分析装置
US7609654B2 (en) 2004-07-01 2009-10-27 Mcdata Corporation Method of evaluating network connectivity between network resources
US7494814B2 (en) 2004-07-13 2009-02-24 Separation Technology, Inc. Apparatus and method for obtaining rapid creamatocrit and caloric content values of milk
US7857760B2 (en) 2004-07-13 2010-12-28 Dexcom, Inc. Analyte sensor
US7196719B2 (en) 2004-07-16 2007-03-27 Vision Robotics Corporation Angled axis machine vision system and method
ES2665788T3 (es) 2004-07-27 2018-04-27 Lsi Medience Corporation Procedimiento de determinación automática de una muestra
US20060026040A1 (en) 2004-07-28 2006-02-02 Reeves Anthony P System and method for providing remote analysis of medical data
EP1626281A1 (fr) 2004-08-03 2006-02-15 The Automation Partnership (Cambridge) Limited Dispositif de pipetage
US20060027586A1 (en) * 2004-08-05 2006-02-09 Longhany Ronald K Freezer storage container with ventilation openings
US20060036619A1 (en) 2004-08-09 2006-02-16 Oren Fuerst Method for accessing and analyzing medically related information from multiple sources collected into one or more databases for deriving illness probability and/or for generating alerts for the detection of emergency events relating to disease management including HIV and SARS, and for syndromic surveillance of infectious disease and for predicting risk of adverse events to one or more drugs
US7690275B1 (en) 2004-08-26 2010-04-06 Elemental Scientific, Inc. Automated sampling device
EP1784505B1 (fr) 2004-09-02 2016-06-22 Bioneer Corporation Appareil miniaturise pour surveillance en temps reel
CN1311239C (zh) 2004-09-07 2007-04-18 李人 免疫层析测试条及其制造方法
KR101214780B1 (ko) 2004-09-15 2012-12-21 인터젠엑스 인크. 미세유동 장치
US7170050B2 (en) 2004-09-17 2007-01-30 Pacific Biosciences Of California, Inc. Apparatus and methods for optical analysis of molecules
US7744821B2 (en) 2004-09-21 2010-06-29 Andreas Hettich Gmbh & Co. Kg Blood bag cup for centrifuges
AT500882A3 (de) * 2004-10-06 2009-12-15 Greiner Bio One Gmbh In-vitro diagnostikum zur speichelvolumsbestimmung
DE102004048864A1 (de) 2004-10-07 2006-04-13 Roche Diagnostics Gmbh Analytisches Testelement mit drahtloser Datenübertragung
JP2006125868A (ja) * 2004-10-26 2006-05-18 Arkray Inc 自動測定用カートリッジおよび測定方法
JP2006125855A (ja) 2004-10-26 2006-05-18 Kusano Kagaku:Kk 分注装置
JP2006125978A (ja) * 2004-10-28 2006-05-18 Arkray Inc 試薬カートリッジ容器用押さえ具
US20060095429A1 (en) 2004-10-29 2006-05-04 Eastman Kodak Company Networked system for routing medical images
EP1812605A4 (fr) * 2004-11-05 2012-04-25 Life Technologies Corp Compositions et procedes permettant d'utiliser des unites d'identification radiofrequence en sciences biologiques
US7604985B2 (en) 2004-11-10 2009-10-20 Becton, Dickinson And Company System and method for determining fill volume in a container
US20120053068A1 (en) 2004-11-18 2012-03-01 Eppendorf Array Technologies Real-time pcr of targets on a micro-array
US20060111620A1 (en) 2004-11-23 2006-05-25 Squilla John R Providing medical services at a kiosk
WO2006083367A2 (fr) 2004-11-23 2006-08-10 Response Biomedical Corporation Dosage immunologique mettant en oeuvre une reaction d'etalonnage interne en deux etapes
KR100581356B1 (ko) 2004-11-25 2006-05-17 재단법인서울대학교산학협력재단 싸이토메트리, 빌로시메트리 및 세포 분류에 사용하기위한 폴리전해질 염다리를 사용하는 마이크로칩
KR100601974B1 (ko) * 2004-11-25 2006-07-18 삼성전자주식회사 비드의 상이한 레이저 흡수에 의한 핵산의 정제 장치 및방법
US20060121491A1 (en) 2004-12-02 2006-06-08 Wolber Paul K Partially degenerate oligonucleotide standards and methods for generating the same
US8263390B2 (en) 2004-12-10 2012-09-11 Universal Bio Research Co., Ltd. Biological material fixed carrier enclosing tip, biological material fixed carrier treatment apparatus, and treatment method thereof
US7978665B1 (en) 2004-12-13 2011-07-12 Verizon Laboratories Inc. Systems and methods for providing connection status and location information in a wireless networking environment
ITMI20042434A1 (it) 2004-12-21 2005-03-21 Paolo Giordano Metodo e dispositivo per l'estrazione rapida di antigeni
JP4203469B2 (ja) 2004-12-24 2009-01-07 アロカ株式会社 液体試料の攪拌装置
CA2598938A1 (fr) 2005-01-26 2006-08-03 Enigma Diagnostics Ltd Procede de reaction
US8614101B2 (en) 2008-05-20 2013-12-24 Rapid Pathogen Screening, Inc. In situ lysis of cells in lateral flow immunoassays
US20060235348A1 (en) 2005-02-14 2006-10-19 Callicoat David N Method of extracting and analyzing the composition of bodily fluids
WO2006087574A2 (fr) 2005-02-19 2006-08-24 Geneform Technologies Limited Amplification isothermique d'acides nucleiques
GB0503836D0 (en) * 2005-02-24 2005-04-06 Axis Shield Asa Method
JP2006276003A (ja) 2005-03-03 2006-10-12 Juki Corp 分注装置
EP1866653A4 (fr) * 2005-03-07 2009-08-26 Novx Systems Inc Analyseur automatise
CA2871777C (fr) 2005-03-10 2015-07-28 Matthew J. Hayes Appareil et methodes de detection de signaux optiques multiples
US7650395B2 (en) 2005-03-18 2010-01-19 Microsoft Corporation Network connectivity management
EP1865305A1 (fr) * 2005-03-31 2007-12-12 Kabushiki Kaisha Toshiba Dispositif de mesure de fluorescence, procédé de mesure de fluorescence, récipient pour mesure de fluorescence, et procédé de fabrication du récipient pour mesure de fluorescence
US20060223178A1 (en) * 2005-04-05 2006-10-05 Tom Barber Devices and methods for magnetic enrichment of cells and other particles
CN103259027A (zh) 2005-04-28 2013-08-21 普罗透斯数字保健公司 药物信息系统
CA2970005C (fr) 2005-05-09 2020-07-28 Biofire Diagnostics, Inc. Appareil et methode d'amplification d'acide nucleique en deux etapes
KR101381331B1 (ko) 2005-05-09 2014-04-04 테라노스, 인코포레이티드 현장진료 유체 시스템 및 그 용도
GB2425974A (en) 2005-05-09 2006-11-15 Orion Diagnostica Oy Sonication of a medium
IES20050304A2 (en) 2005-05-11 2006-11-15 Haemoglobal Biotech Ltd A mobile chemistry and haematology analyser with an intergrated diagnostic databank
JP4520359B2 (ja) * 2005-05-13 2010-08-04 日立ソフトウエアエンジニアリング株式会社 粒子捕捉装置、並びに粒子配列方法及び粒子配列装置
JP4657803B2 (ja) 2005-05-19 2011-03-23 富士フイルム株式会社 送液システム及びその送液方法並びに流路ユニット。
GB0510362D0 (en) 2005-05-20 2005-06-29 Univ Greenwich Device for detecting mycotoxins
EP1888739B1 (fr) * 2005-05-24 2021-08-11 Lee H. Angros Appareil automatique et procédé de traitement d'échantillons biologiques sur lames porte-échantillon
US20060281187A1 (en) * 2005-06-13 2006-12-14 Rosedale Medical, Inc. Analyte detection devices and methods with hematocrit/volume correction and feedback control
WO2006138743A2 (fr) * 2005-06-23 2006-12-28 Bioprocessors Corp. Dispositif de transfert de fluide
US20070031283A1 (en) * 2005-06-23 2007-02-08 Davis Charles Q Assay cartridges and methods for point of care instruments
CA2613078A1 (fr) 2005-06-24 2007-01-04 Board Of Regents, The University Of Texas System Systemes et procedes faisant appel a des cartouches autonomes comprenant des systemes de detection et des systemes de distribution de fluides
US20070004577A1 (en) 2005-06-29 2007-01-04 Gabor Lederer Centrifuge assembly
US7663750B2 (en) 2005-06-30 2010-02-16 Applied Biosystems, Llc Two-dimensional spectral imaging system
JP2007017354A (ja) 2005-07-08 2007-01-25 Sumitomo Bakelite Co Ltd 化学反応検出システム
JP2007032234A (ja) 2005-07-29 2007-02-08 Sekisui Chem Co Ltd 二重床構造
US7422554B2 (en) 2005-08-10 2008-09-09 The Drucker Company, Inc. Centrifuge with aerodynamic rotor and bucket design
US9285297B2 (en) * 2005-08-22 2016-03-15 Applied Biosystems, Llc Device, system, and method for depositing processed immiscible-fluid-discrete-volumes
EP2061599A4 (fr) 2005-08-24 2014-01-22 Telechemistry Oy Procede permettant de tester un echantillon de liquide, unite de test et systeme automatise d'une pluralite d'unites de test
US7757778B2 (en) * 2005-08-24 2010-07-20 Calderwood James A Ripper boot
DE102005047131A1 (de) * 2005-09-30 2007-04-12 Evotec Technologies Gmbh Verfahren und Vorrichtung zur Manipulation von sedimentierenden Partikeln
FR2891625B1 (fr) 2005-10-03 2007-12-21 Francois Melet Analyseur compact de biochimie seche pour l'analyse d'echantillons sanguins.
US7733224B2 (en) 2006-06-30 2010-06-08 Bao Tran Mesh network personal emergency response appliance
US8652421B2 (en) 2005-11-03 2014-02-18 Emd Millipore Corporation Immunoassay product and process
US7581660B2 (en) 2005-11-09 2009-09-01 Hamilton Bonaduz Ag Drip-resistant pipetting device and drip-resistant pipetting method
GB0523231D0 (en) 2005-11-15 2005-12-21 Redfern Jonathan Liquid photometer using disposable pipette tip vessel
US20070118399A1 (en) 2005-11-22 2007-05-24 Avinash Gopal B System and method for integrated learning and understanding of healthcare informatics
AU2006320739B2 (en) 2005-11-28 2012-03-29 Pacific Biosciences Of California, Inc. Uniform surfaces for hybrid material substrates and methods for making and using same
GB2432660A (en) 2005-11-29 2007-05-30 Bacterioscan Ltd System for counting bacteria and determining their susceptibility to antibiotics
JP2007152157A (ja) 2005-11-30 2007-06-21 Hitachi Koki Co Ltd 遠心機
US20070125677A1 (en) 2005-12-06 2007-06-07 Neil Oronsky Thermal and/or light protective container assemblies and their methods of use
US20070131870A1 (en) * 2005-12-12 2007-06-14 Combisep Multiplexed CE fluorescence system
AU2006330913B2 (en) * 2005-12-21 2011-10-27 Meso Scale Technologies, Llc Assay modules having assay reagents and methods of making and using same
CN101379385A (zh) 2005-12-22 2009-03-04 霍尼韦尔国际公司 便携式样品分析盒
WO2007075919A2 (fr) 2005-12-22 2007-07-05 Honeywell International Inc. Systeme d'analyseur portatif d'echantillons
JP2007178328A (ja) * 2005-12-28 2007-07-12 Shimadzu Corp 反応容器キット及び反応容器処理装置
JP5178528B2 (ja) 2005-12-29 2013-04-10 アボット ポイント オブ ケア インコーポレイテッド 分子診断用増幅システムおよび方法
CN103499466B (zh) * 2006-01-18 2017-04-12 阿戈斯治疗公司 用于处理封闭容器中的样品的系统和方法以及相关装置
US7876935B2 (en) 2006-01-30 2011-01-25 Protedyne Corporation Sample processing apparatus with a vision system
US7711800B2 (en) 2006-01-31 2010-05-04 Microsoft Corporation Network connectivity determination
WO2007092713A2 (fr) 2006-02-02 2007-08-16 Trustees Of The University Of Pennsylvania Système microfluidique et procédé d'analyse de l'expression génique dans des échantillons contenant des cellules et procédé de détection d'une maladie
US20070192138A1 (en) 2006-02-16 2007-08-16 Motoaki Saito Medical record system in a wide-area network environment
WO2007105198A2 (fr) 2006-03-10 2007-09-20 Hadas Lewy Échantillonnage et analyse automatiques au moyen d'un échantilloneur personnel
WO2007105726A1 (fr) 2006-03-14 2007-09-20 Nemoto Kyorindo Co., Ltd. Système d'imagerie médicale
US8741230B2 (en) 2006-03-24 2014-06-03 Theranos, Inc. Systems and methods of sample processing and fluid control in a fluidic system
EP3088083B1 (fr) 2006-03-24 2018-08-01 Handylab, Inc. Méthode pour la mise en oeuvre de pcr au moyen d'une cartouche avec plusieures pistes
JP5371741B2 (ja) 2006-04-24 2013-12-18 フィッツ、リチャード 体液分析装置、当該装置を含むシステム
US7624557B2 (en) 2006-05-02 2009-12-01 Box Partition Technologies, Inc. Assembling machine with continuous periodic assembly motion
JP2009535635A (ja) 2006-05-03 2009-10-01 エヌツェーエル ニュー コンセプト ラブ ゲーエムベーハー 化学的、生化学的、生物学的および物理学的分析、反応、アッセイなどのためのデバイスおよび方法
US8007999B2 (en) 2006-05-10 2011-08-30 Theranos, Inc. Real-time detection of influenza virus
CA2657970A1 (fr) 2006-05-17 2007-11-29 Luminex Corporation Systemes de type cytometres en flux sur circuits integres pour analyser des particules marquees de maniere fluorescente
US8232091B2 (en) 2006-05-17 2012-07-31 California Institute Of Technology Thermal cycling system
JP2007309889A (ja) 2006-05-22 2007-11-29 Olympus Corp 異物検出装置及び異物検出方法
JP2007322324A (ja) 2006-06-02 2007-12-13 Olympus Corp 分析装置
DE602007003832D1 (de) 2006-06-06 2010-01-28 Roche Diagnostics Gmbh Gebrauchsfertiges sammelgefäss für vollblut
KR100772969B1 (ko) 2006-06-08 2007-11-02 양현진 원심분리기 및 원심분리방법
WO2007146443A2 (fr) 2006-06-14 2007-12-21 Oldenburg Kevin R Ph D dispositifs de cyclage thermique et procédés d'utilisation de ceux-ci
WO2008005464A2 (fr) 2006-06-30 2008-01-10 University Of Southern California Étalons de référence internes quantifiables pour immunohistochimie et leurs utilisations
US7972786B2 (en) 2006-07-07 2011-07-05 Brandeis University Detection and analysis of influenza virus
JP2009544083A (ja) 2006-07-13 2009-12-10 アイ−スタット コーポレイション 医療データ取得および患者管理のシステムおよび方法
SE531041C2 (sv) 2006-07-17 2008-11-25 Hemocue Ab Räkning av trombocyter
SE530192C2 (sv) 2006-07-19 2008-03-25 Hemocue Ab Apparat för avbildning av prov där provhållaren är flyttbar medelst magnetisk växelverkan
US20080020469A1 (en) 2006-07-20 2008-01-24 Lawrence Barnes Method for scheduling samples in a combinational clinical analyzer
DE102006034245C5 (de) 2006-07-21 2014-05-28 Stratec Biomedical Systems Ag Positioniereinrichtung zur Positionierung von Pipetten
EP1882948A2 (fr) * 2006-07-28 2008-01-30 Qiagen GmbH Dispositif destiné au traitement d échantillons
EP1892531B1 (fr) 2006-08-22 2017-04-05 Sysmex Corporation Analyseur d'échantillon
JP4979305B2 (ja) 2006-08-22 2012-07-18 シスメックス株式会社 分析装置
US7787681B2 (en) 2006-08-25 2010-08-31 The Trustees Of Columbia University In The City Of New York Systems and methods for robotic transport
JP2008064701A (ja) 2006-09-11 2008-03-21 Matsushita Electric Ind Co Ltd 回転分析デバイス及び計量方法及び検査方法
US7674616B2 (en) 2006-09-14 2010-03-09 Hemosense, Inc. Device and method for measuring properties of a sample
US7745149B2 (en) * 2006-09-14 2010-06-29 National Taiwan University Tumor markers for ovarian cancer diagnosis
ATE479779T1 (de) * 2006-09-29 2010-09-15 Leukocare Ag Verfahren zum nachweis einer aktivierung des immunsystems oder des ausmasses von zelltod
US20100240544A1 (en) 2006-09-29 2010-09-23 Liu David J Aptamer biochip for multiplexed detection of biomolecules
CN101523212B (zh) 2006-10-12 2015-04-01 皇家飞利浦电子股份有限公司 具有试剂层的快速生物传感器
US7312042B1 (en) 2006-10-24 2007-12-25 Abbott Diabetes Care, Inc. Embossed cell analyte sensor and methods of manufacture
US7662344B2 (en) 2006-10-24 2010-02-16 Viaflo Corporation Locking pipette tip and mounting shaft
US20110001036A1 (en) 2006-10-24 2011-01-06 Koninklijke Philips Electronics N.V. system for imaging an object
US7662343B2 (en) 2006-10-24 2010-02-16 Viaflo Corporation Locking pipette tip and mounting shaft
US7910302B2 (en) 2006-10-27 2011-03-22 Complete Genomics, Inc. Efficient arrays of amplified polynucleotides
WO2008055257A2 (fr) 2006-11-02 2008-05-08 Vectrant Technologies Inc. Cartouche destinée à effectuer des dosages diagnostiques
US20080113391A1 (en) 2006-11-14 2008-05-15 Ian Gibbons Detection and quantification of analytes in bodily fluids
DE102006057300A1 (de) 2006-12-05 2008-06-19 Siemens Ag Anordnung zur Aufbereitung einer Mehrzahl von Proben für eine Analyse
WO2008077007A1 (fr) 2006-12-19 2008-06-26 Cytyc Corporation Procédé d'analyse de la teneur en sang d'échantillons cytologiques
GB0625595D0 (en) 2006-12-21 2007-01-31 Oxford Gene Tech Ip Ltd Sample analyser
RU2365622C2 (ru) * 2006-12-22 2009-08-27 Закрытое акционерное общество "Научно-исследовательский институт Аджиномото-Генетика" (ЗАО АГРИ) СПОСОБ ПРОДУКЦИИ ПУРИНОВЫХ НУКЛЕОЗИДОВ И НУКЛЕОТИДОВ МЕТОДОМ ФЕРМЕНТАЦИИ С ИСПОЛЬЗОВАНИЕМ БАКТЕРИЙ, ПРИНАДЛЕЖАЩИХ К РОДУ Escherichia ИЛИ Bacillus
US7955867B2 (en) * 2007-01-31 2011-06-07 Millipore Corporation High throughput cell-based assays, methods of use and kits
WO2008115632A2 (fr) 2007-02-09 2008-09-25 The Regents Of The University Of California Procédé de recombinaison de séquences d'adn et compositions s'y rapportant
US20090137047A1 (en) 2007-03-02 2009-05-28 John Frederick Regan Automated Diagnostic Kiosk for Diagnosing Diseases
US20080228107A1 (en) 2007-03-12 2008-09-18 Venkateshwara N Reddy Bio-testing booth
US8143554B2 (en) 2007-03-16 2012-03-27 Amerigon Incorporated Air warmer
US20090215157A1 (en) 2007-03-27 2009-08-27 Searete Llc Methods for pathogen detection
CA2681738A1 (fr) 2007-03-27 2008-10-02 Theranostics Health, Inc. Systeme, procede et produit de programmation logicielle pour la manipulation de tests theranostiques
US8557588B2 (en) 2007-03-27 2013-10-15 Schlumberger Technology Corporation Methods and apparatus for sampling and diluting concentrated emulsions
GB0706281D0 (en) 2007-03-30 2007-05-09 Guy S And St Thomas Nhs Founda Apparatus and method for recovering fluid from a fluid absorbing element
US8877507B2 (en) 2007-04-06 2014-11-04 Qiagen Gaithersburg, Inc. Ensuring sample adequacy using turbidity light scattering techniques
US8387811B2 (en) 2007-04-16 2013-03-05 Bd Diagnostics Pierceable cap having piercing extensions
EP2140412B1 (fr) 2007-04-23 2018-12-12 Samsung Electronics Co., Ltd. Système et procédé de télédiagnostic médical
WO2008149518A1 (fr) 2007-05-30 2008-12-11 Nemoto Kyorindo Co., Ltd. Dispositif d'injection de liquide chimique, système d'imagerie fluoroscopique et programme d'ordinateur
JP4876027B2 (ja) 2007-05-30 2012-02-15 株式会社日立ハイテクノロジーズ 分注装置
EP2000528A1 (fr) * 2007-06-04 2008-12-10 The Automation Partnership (Cambridge) Limited Appareil d'agitation pour incubateur de culture cellulaire ou similaires
WO2009002447A1 (fr) 2007-06-21 2008-12-31 Gen-Probe Incorporated Instrument et réceptacles pour l'exécution de procédés
JP4982266B2 (ja) 2007-06-22 2012-07-25 株式会社日立ハイテクノロジーズ 分注処理装置
US20090004754A1 (en) 2007-06-26 2009-01-01 Oldenburg Kevin R Multi-well reservoir plate and methods of using same
US9186677B2 (en) 2007-07-13 2015-11-17 Handylab, Inc. Integrated apparatus for performing nucleic acid extraction and diagnostic testing on multiple biological samples
US8133671B2 (en) 2007-07-13 2012-03-13 Handylab, Inc. Integrated apparatus for performing nucleic acid extraction and diagnostic testing on multiple biological samples
US8287820B2 (en) 2007-07-13 2012-10-16 Handylab, Inc. Automated pipetting apparatus having a combined liquid pump and pipette head system
US20090148941A1 (en) 2007-07-30 2009-06-11 Peter Florez Disposable mini-bioreactor device and method
US8158430B1 (en) 2007-08-06 2012-04-17 Theranos, Inc. Systems and methods of fluidic sample processing
JP2010536371A (ja) 2007-08-21 2010-12-02 ノダリティ，インコーポレイテッド 診断方法、予後および治療方法
US7843560B2 (en) 2007-08-31 2010-11-30 Dow Global Technologies Inc. Stable turbidity calibration standards
US8783484B2 (en) 2007-08-31 2014-07-22 Saint-Gobain Performance Plastics Corporation Septa
EP2205968B1 (fr) 2007-10-02 2013-11-20 Theranos, Inc. Dispositifs modulaires à utiliser sur place et leurs utilisations
EP2205717B1 (fr) 2007-10-03 2017-08-16 3M Innovative Properties Company Procédé de concentration de micro-organismes
US9083722B2 (en) 2007-10-05 2015-07-14 Qualcomm Incorporated Session initiation protocol registration with ping
WO2009049171A2 (fr) * 2007-10-10 2009-04-16 Pocared Diagnostics Ltd. Système utilisé pour identifier des bactéries dans l'urine
US7947234B2 (en) 2007-10-17 2011-05-24 Rainin Instrument, Llc Liquid end assembly for a handheld multichannel pipette with adjustable nozzle spacing
US20110034758A1 (en) 2007-10-23 2011-02-10 Vered Shany Cartridge For A Biological Sample
EP2210080B1 (fr) * 2007-10-24 2015-01-28 Biomarker Strategies, Llc Procédés et dispositifs améliorés pour l'analyse cellulaire
US20090117009A1 (en) 2007-11-02 2009-05-07 Richard Cote Multi-channel electronic pipettor
US8463167B2 (en) 2007-11-09 2013-06-11 Canon Kabushiki Kaisha Image heating apparatus and image heating rotational body to be mounted on the image heating apparatus
US20090124284A1 (en) 2007-11-14 2009-05-14 Shimon Scherzer System and method for providing seamless broadband internet access to web applications
EP2220477B1 (fr) 2007-12-18 2011-09-21 CaridianBCT, Inc. Appareil de traitement de sang avec diffuseur scellé dans un appareil de commande optique
CN101925821B (zh) 2008-01-22 2014-09-24 株式会社岛津制作所 测定装置及具有其的液体提取测定系统
US20090204435A1 (en) 2008-01-31 2009-08-13 Brian Gale System for automating medical imaging diagnostic service delivery
WO2009099512A2 (fr) 2008-02-04 2009-08-13 Micropoint Biosciences, Inc. Rotor pour analyseur centrifuge de fluides
CN107132185B (zh) 2008-02-05 2020-05-29 普凯尔德诊断技术有限公司 用于鉴定生物样品中细菌的系统
US8034568B2 (en) 2008-02-12 2011-10-11 Nugen Technologies, Inc. Isothermal nucleic acid amplification methods and compositions
US8187808B2 (en) 2008-02-29 2012-05-29 Northwestern University Barriers for facilitating biological reactions
JP5198094B2 (ja) 2008-03-07 2013-05-15 シスメックス株式会社 分析装置
US7850917B2 (en) 2008-03-11 2010-12-14 Ortho-Clinical Diagnostics, Inc. Particle agglutination in a tip
US8137920B2 (en) 2008-03-20 2012-03-20 Abaxis, Inc. Multi-wavelength analyses of sol-particle specific binding assays
CA2719625C (fr) 2008-03-26 2019-02-26 Theranos, Inc. Procedes et systemes de determination de resultats cliniques
CA2719747C (fr) 2008-03-28 2018-02-20 Pacific Biosciences Of California, Inc. Compositions et procedes pour le sequencage d'acide nucleique
WO2009123000A1 (fr) 2008-03-31 2009-10-08 シスメックス株式会社 Dispositif de traitement de cellules, dispositif de préparation d'échantillons et dispositif d'analyse de cellules
JP5749156B2 (ja) * 2008-04-05 2015-07-15 シングル セル テクノロジー, インコーポレイテッドSingle Cell Technology, Inc. 生理活性物質の生産のための単一細胞を選抜する方法
EP2112514A1 (fr) 2008-04-24 2009-10-28 bioMérieux BV Procédé et appareil de vérification du fluide dans l'extrémité d'une pipette
US20090274348A1 (en) 2008-04-30 2009-11-05 Ortho-Clinical Diagnostics, Inc. Immunodiagnostic test apparatus having at least one imager to provide agglutination evaluations during centrifugration cycle
US8029742B2 (en) 2008-05-05 2011-10-04 Integra Biosciences Corp. Multi-channel pipettor with repositionable tips
JP2010133924A (ja) 2008-10-28 2010-06-17 Sysmex Corp 液体吸引機構および試料分析装置
EP2304436A1 (fr) 2008-07-10 2011-04-06 Nodality, Inc. Procédés de diagnostic, pronostic et traitement
KR100978912B1 (ko) 2008-07-10 2010-08-31 주식회사 한랩 자동 평형형 원심분리기
US20100015690A1 (en) 2008-07-16 2010-01-21 Ortho-Clinical Diagnostics, Inc. Use of fluid aspiration/dispensing tip as a microcentrifuge tube
ES2451541T3 (es) 2008-07-16 2014-03-27 International Technidyne Corporation Aparato a base de cubeta para medición y ensayo de la coagulación sanguínea
US9779213B2 (en) 2008-07-25 2017-10-03 Fundacao D. Anna Sommer Champalimaud E Dr. Carlos Montez Champalimaud System for evaluating a pathological stage of prostate cancer
EP2214011B1 (fr) 2008-08-01 2019-01-02 Sysmex Corporation Appareil d'analyse d'échantillon sanguin
JP5465850B2 (ja) 2008-08-01 2014-04-09 シスメックス株式会社 試料分析システム
US9034257B2 (en) 2008-10-27 2015-05-19 Nodality, Inc. High throughput flow cytometry system and method
GB2497007B (en) 2008-11-07 2013-08-07 Sequenta Inc Methods of monitoring disease conditions by analysis of the full repertoire of the V-D junction or D-J junction sequences of an individual
US8309306B2 (en) 2008-11-12 2012-11-13 Nodality, Inc. Detection composition
US8900878B2 (en) 2008-11-28 2014-12-02 Roche Molecular Systems Inc. Pipetting device, modular pipetting unit, pipetting system and method for pipetting of fluid samples
CA2745732C (fr) 2008-12-05 2014-02-11 F. Hoffmann-La Roche Ag Procede de fabrication d'un ensemble de recipients a reactifs et ensemble de recipients a reactifs
JP2010145252A (ja) 2008-12-18 2010-07-01 Nippon Soken Inc 液体燃料性状検出装置
WO2010069080A1 (fr) 2008-12-19 2010-06-24 Stemcell Technologies Inc. Appareil de filtration et système de plaque de filtration
WO2010090857A2 (fr) 2009-01-21 2010-08-12 Vertex Pharmaceuticals Incorporated Procédés d'amplification d'acides nucléiques du virus de l'hépatite c
JP2010175342A (ja) 2009-01-28 2010-08-12 Hitachi High-Technologies Corp 自動分析装置及び反応容器
US20100215644A1 (en) 2009-02-25 2010-08-26 Nodality, Inc. A Delaware Corporation Analysis of nodes in cellular pathways
US20100246416A1 (en) 2009-03-25 2010-09-30 Amit Sinha Systems and methods for remote testing of wireless lan access points
US8320985B2 (en) 2009-04-02 2012-11-27 Empire Technology Development Llc Touch screen interfaces with pulse oximetry
CN102414554B (zh) 2009-04-22 2014-11-26 威斯康星校友研究基金会 采用液晶的分析物检测
GB2473868A (en) 2009-09-28 2011-03-30 Invitrogen Dynal As Apparatus and method of automated processing of biological samples
EP2253958B1 (fr) 2009-05-18 2013-04-17 F. Hoffmann-La Roche AG Système microfluidique basé sur la force centrifuge et méthode pour l'analyse automatique d'échantillons
DE102009022972A1 (de) 2009-05-28 2010-12-02 Gea Westfalia Separator Gmbh Zentrifuge mit einem Schmiermittelsystem
US8426214B2 (en) 2009-06-12 2013-04-23 University Of Washington System and method for magnetically concentrating and detecting biomarkers
CA3083798C (fr) 2009-07-27 2023-08-15 Meso Scale Technologies, Llc Appareils, consommables et procedes d'essai
EP2311563A1 (fr) 2009-08-07 2011-04-20 F. Hoffmann-La Roche AG Unités de traitement et procédé pour le traitement d'échantillons liquides
US7982201B2 (en) 2009-09-08 2011-07-19 Jadak, Llc System and method for detection of liquid level in a vessel
CA3081708C (fr) 2009-10-19 2023-10-03 Theranos Ip Company, Llc Systeme de capture et d'analyse integre de donnees de sante
US8372657B2 (en) 2009-10-20 2013-02-12 Agency For Science, Technology, And Research Microfluidic system for detecting a biological entity in a sample
EP2490814B1 (fr) 2009-10-22 2015-01-14 Brian Page Pipette, appareil et kit pour la mesure de la lumière et procédé correspondant
US9521055B2 (en) 2009-11-13 2016-12-13 Verizon Patent And Licensing Inc. Network connectivity management
US20120206587A1 (en) 2009-12-04 2012-08-16 Orscan Technologies Ltd System and method for scanning a human body
FI4060325T3 (fi) 2009-12-07 2024-09-25 Meso Scale Technologies Llc Määrityskasetin lukija
US8748186B2 (en) 2009-12-22 2014-06-10 Abbott Laboratories Method for performing a blood count and determining the morphology of a blood smear
US9486803B2 (en) 2010-01-22 2016-11-08 Biotix, Inc. Pipette tips
JP5564980B2 (ja) 2010-02-23 2014-08-06 日本電気株式会社 セキュリティスクリーニングシステムおよびセキュリティスクリーニング方法
WO2011106315A1 (fr) 2010-02-23 2011-09-01 Rheonix, Inc. Appareil de dosage biologique autonome, procédés et applications
US20110213579A1 (en) 2010-02-26 2011-09-01 Henke Tom L Method and apparatus for verifying test results
US20110213564A1 (en) 2010-02-26 2011-09-01 Henke Tom L Method and apparatus for code verified testing
WO2011106512A1 (fr) 2010-02-26 2011-09-01 Quickcheck Health, Inc. Procédé et appareil pour essai vérifié par code
US20110213619A1 (en) 2010-02-26 2011-09-01 Henke Tom L Method and system for online medical diagnosis
US20110218428A1 (en) 2010-03-04 2011-09-08 Medical Scan Technologies, Inc. System and Method for Three Dimensional Medical Imaging with Structured Light
US8588807B2 (en) 2010-04-28 2013-11-19 Palm, Inc. System and method for dynamically managing connections using a coverage database
CN103725591A (zh) 2010-07-23 2014-04-16 贝克曼考尔特公司 盒装载单元
US20120059664A1 (en) 2010-09-07 2012-03-08 Emil Markov Georgiev System and method for management of personal health and wellness
US20120083501A1 (en) 2010-09-24 2012-04-05 Hunt Kevin W Compounds for treating neurodegenerative diseases
WO2012054589A2 (fr) 2010-10-22 2012-04-26 T2 Biosystems, Inc. Dispositifs contenant des conduits et procédés pour le traitement et la détection d'analytes
JP5950920B2 (ja) 2010-10-22 2016-07-13 ティー２ バイオシステムズ インコーポレイテッド 検体の検出のためのｎｍｒシステムおよび方法
US8804114B2 (en) 2010-11-03 2014-08-12 Pocared Diagnostics Ltd. Optical cup
CN108761108B (zh) 2010-11-23 2022-06-07 安德鲁联合有限公司 容积校准、处理流体和操纵移液管的方法
CA2819126A1 (fr) 2010-12-03 2012-06-07 Abbott Point Of Care Inc. Dispositif doseur d'echantillon et dispositif d'analyse comportant la dilution integree de l'echantillon
US20130243794A1 (en) 2010-12-03 2013-09-19 Beth Israel Deaconess Medical Center, Inc. Methods for predicting and treating infection-induced illnesses and predicting the severity of infection-induced illnesses
JP6087293B2 (ja) 2011-01-06 2017-03-01 メソ スケール テクノロジーズ エルエルシー アッセイカートリッジ及びその使用方法
EP4024029A3 (fr) 2011-01-21 2022-09-14 Labrador Diagnostics LLC Systèmes et procédés de maximisation d'utilisation d'échantillon
US9168523B2 (en) 2011-05-18 2015-10-27 3M Innovative Properties Company Systems and methods for detecting the presence of a selected volume of material in a sample processing device
CN203941178U (zh) 2011-05-20 2014-11-12 珀金埃尔默保健科学公司 实验室部件和液体装卸系统及辅助性可流动材料装卸系统
EP2746395B1 (fr) 2011-09-08 2017-11-29 Kabushiki Kaisha DNAFORM Ensemble d'amorces, procédé d'amplification d'une séquence d'acide nucléique cible à l'aide de celui-ci, et procédé de détection d'un acide nucléique muté à l'aide de celui-ci
US8435738B2 (en) 2011-09-25 2013-05-07 Theranos, Inc. Systems and methods for multi-analysis
WO2013043203A2 (fr) 2011-09-25 2013-03-28 Theranos, Inc. Systèmes et procédés pour analyse multifonction
US8840838B2 (en) 2011-09-25 2014-09-23 Theranos, Inc. Centrifuge configurations
US20140170735A1 (en) * 2011-09-25 2014-06-19 Elizabeth A. Holmes Systems and methods for multi-analysis
US9632102B2 (en) 2011-09-25 2017-04-25 Theranos, Inc. Systems and methods for multi-purpose analysis
US9664702B2 (en) 2011-09-25 2017-05-30 Theranos, Inc. Fluid handling apparatus and configurations
US20130074614A1 (en) 2011-09-25 2013-03-28 Theranos, Inc., a Delaware Corporation Container configurations
US8475739B2 (en) 2011-09-25 2013-07-02 Theranos, Inc. Systems and methods for fluid handling
US9619627B2 (en) 2011-09-25 2017-04-11 Theranos, Inc. Systems and methods for collecting and transmitting assay results
US8380541B1 (en) 2011-09-25 2013-02-19 Theranos, Inc. Systems and methods for collecting and transmitting assay results
US9268915B2 (en) 2011-09-25 2016-02-23 Theranos, Inc. Systems and methods for diagnosis or treatment
US20130080071A1 (en) 2011-09-25 2013-03-28 Theranos, Inc., a Delaware Corporation Systems and methods for sample processing and analysis
US9810704B2 (en) 2013-02-18 2017-11-07 Theranos, Inc. Systems and methods for multi-analysis
US10012664B2 (en) 2011-09-25 2018-07-03 Theranos Ip Company, Llc Systems and methods for fluid and component handling
US9250229B2 (en) * 2011-09-25 2016-02-02 Theranos, Inc. Systems and methods for multi-analysis
US11249799B2 (en) 2011-09-26 2022-02-15 Labrador Diagnostics Llc Methods, systems, and devices for real time execution and optimization of concurrent test protocols on a single device
US20160077015A1 (en) 2011-09-25 2016-03-17 Theranos, Inc. Systems and methods for multi-analysis
US8392585B1 (en) 2011-09-26 2013-03-05 Theranos, Inc. Methods and systems for facilitating network connectivity
US20140335505A1 (en) 2011-09-25 2014-11-13 Theranos, Inc. Systems and methods for collecting and transmitting assay results
US20160069919A1 (en) 2011-09-25 2016-03-10 Theranos, Inc. Systems and methods for multi-analysis
US20160320381A1 (en) 2011-09-25 2016-11-03 Theranos, Inc. Systems and methods for multi-analysis
CN103946364B (zh) 2011-09-25 2018-04-24 赛拉诺斯知识产权有限责任公司 用于多重分析的系统和方法
US20140308661A1 (en) 2011-09-25 2014-10-16 Theranos, Inc. Systems and methods for multi-analysis
WO2013053855A1 (fr) 2011-10-11 2013-04-18 Qiagen Gmbh Procédé de traitement d'échantillon et cartouche de traitement d'échantillon
JP5854218B2 (ja) 2012-01-24 2016-02-09 日立工機株式会社 遠心分離機
US9073052B2 (en) 2012-03-30 2015-07-07 Perkinelmer Health Sciences, Inc. Lab members and liquid handling systems and methods including same
US20150130463A1 (en) 2012-06-25 2015-05-14 T2 Biosystems, Inc. Portable device for nmr based analysis of rheological changes in liquid samples
US9389229B2 (en) 2012-07-18 2016-07-12 Theranos, Inc. Methods for detecting and measuring aggregation
MX381057B (es) 2012-07-18 2025-03-12 Labrador Diagnostics Llc Centrífuga compacta de alta velocidad para utilizarse con pequeños volúmenes de muestra.
AU2013315800A1 (en) 2012-09-11 2015-03-12 Theranos Ip Company, Llc Information management systems and methods using a biological signature
CN102974474B (zh) 2012-11-13 2014-02-26 湖南航天机电设备与特种材料研究所 一种超速离心机
US20140342371A1 (en) 2012-12-05 2014-11-20 Theranos, Inc. Bodily Fluid Sample Collection and Transport
US9051599B2 (en) 2012-12-10 2015-06-09 Theranos, Inc. Rapid, low-sample-volume cholesterol and triglyceride assays
US20140170678A1 (en) 2012-12-17 2014-06-19 Leukodx Ltd. Kits, compositions and methods for detecting a biological condition
CA2898477A1 (fr) 2013-02-18 2014-08-21 Theranos, Inc. Systemes et procedes d'analyse multiple
US20160054343A1 (en) 2013-02-18 2016-02-25 Theranos, Inc. Systems and methods for multi-analysis
WO2014145291A1 (fr) 2013-03-15 2014-09-18 Theranos, Inc. Amplification d'acide nucléique
SG11201507272RA (en) 2013-03-15 2015-10-29 Theranos Inc Nuclei acid amplification
US9359632B2 (en) 2013-03-15 2016-06-07 Theranos, Inc. Devices, systems and methods for sample preparation
EP3042208A4 (fr) 2013-09-06 2017-04-19 Theranos, Inc. Systèmes et procédés pour détection de maladies infectieuses
MX2016002797A (es) 2013-09-06 2016-05-26 Theranos Inc Dispositivos, sistemas, metodos y equipos para recibir un hisopo.
US10828636B2 (en) 2016-10-25 2020-11-10 Fannin Partners Llc Automated remotely instructed driving of an assay

Also Published As

Publication number Publication date
US9435793B2 (en) 2016-09-06
RU2010117267A (ru) 2011-11-10
RU2013127796A (ru) 2014-12-27
US20180231536A1 (en) 2018-08-16
IL223604A0 (en) 2013-02-03
BRPI0820328B8 (pt) 2021-07-27
IL223601A0 (en) 2013-02-03
US11092593B2 (en) 2021-08-17
US11899010B2 (en) 2024-02-13
KR20150063603A (ko) 2015-06-09
CN103323610B (zh) 2016-12-28
US20120149035A1 (en) 2012-06-14
IL204877A0 (en) 2010-11-30
IL223599A (en) 2014-11-30
JP2014186038A (ja) 2014-10-02
MX2010003578A (es) 2010-06-09
IL223603A0 (en) 2013-02-03
US11137391B2 (en) 2021-10-05
US20130274139A1 (en) 2013-10-17
CA3042430C (fr) 2022-10-11
US20130252320A1 (en) 2013-09-26
ES2447875T3 (es) 2014-03-13
JP2013145247A (ja) 2013-07-25
EP4450163A3 (fr) 2024-10-30
MX352987B (es) 2017-12-15
US20150355169A1 (en) 2015-12-10
AU2013205047B2 (en) 2015-01-22
AU2013205047A1 (en) 2013-05-16
CN104297507A (zh) 2015-01-21
CN104297506A (zh) 2015-01-21
KR101670621B1 (ko) 2016-10-28
HK1206422A1 (en) 2016-01-08
US8697377B2 (en) 2014-04-15
JP2018136345A (ja) 2018-08-30
CA3170924A1 (fr) 2009-04-09
CA2934220A1 (fr) 2009-04-09
CN101874205B (zh) 2014-10-01
AU2008308686A1 (en) 2009-04-09
US10900958B2 (en) 2021-01-26
SG10201606120XA (en) 2016-09-29
US20160266108A1 (en) 2016-09-15
US20150377871A1 (en) 2015-12-31
CA3138078C (fr) 2024-02-13
US20180238864A1 (en) 2018-08-23
CN104297507B (zh) 2017-10-10
IL223602A0 (en) 2013-02-03
RU2669767C2 (ru) 2018-10-16
US11061022B2 (en) 2021-07-13
CN104502579A (zh) 2015-04-08
EP3756767A1 (fr) 2020-12-30
IL260063A (en) 2018-07-31
CA3138078A1 (fr) 2009-04-09
US10634667B2 (en) 2020-04-28
JP2016186495A (ja) 2016-10-27
IL223601A (en) 2017-10-31
KR20100097103A (ko) 2010-09-02
EP2657699A1 (fr) 2013-10-30
SG188082A1 (en) 2013-03-28
JP2023181301A (ja) 2023-12-21
BRPI0820328B1 (pt) 2021-01-05
AU2008308686B2 (en) 2015-01-22
EP2657699B1 (fr) 2017-03-22
JP5511669B2 (ja) 2014-06-04
JP2021103185A (ja) 2021-07-15
CN108333379A (zh) 2018-07-27
US20160161513A1 (en) 2016-06-09
EP3181228B1 (fr) 2020-07-29
IL223599A0 (en) 2013-02-03
BR122020017678B1 (pt) 2021-08-03
US20160139138A1 (en) 2016-05-19
CN101874205A (zh) 2010-10-27
RU2540424C2 (ru) 2015-02-10
CA2934220C (fr) 2019-11-05
AU2013205047A8 (en) 2013-05-30
CA2701794C (fr) 2017-10-31
CN103323610A (zh) 2013-09-25
BRPI0820328A2 (pt) 2016-08-16
US10670588B2 (en) 2020-06-02
US20130244898A1 (en) 2013-09-19
US20150198588A1 (en) 2015-07-16
US20140335506A1 (en) 2014-11-13
US20160266163A1 (en) 2016-09-15
CN104297506B (zh) 2017-05-03
KR20130119006A (ko) 2013-10-30
HK1150175A1 (en) 2011-11-04
IL223603A (en) 2015-08-31
EP3756767B1 (fr) 2024-05-01
US20160025721A1 (en) 2016-01-28
US20210156848A1 (en) 2021-05-27
ES2818194T3 (es) 2021-04-09
CA3042430A1 (fr) 2009-04-09
US20090088336A1 (en) 2009-04-02
JP7412215B2 (ja) 2024-01-12
JP2020073941A (ja) 2020-05-14
EP3181228A1 (fr) 2017-06-21
HK1206424A1 (en) 2016-01-08
KR20180032684A (ko) 2018-03-30
US11199538B2 (en) 2021-12-14
EP2205968A4 (fr) 2010-09-29
EP3756767C0 (fr) 2024-05-01
US20170016904A1 (en) 2017-01-19
KR101669323B1 (ko) 2016-10-25
WO2009046227A1 (fr) 2009-04-09
KR20160126090A (ko) 2016-11-01
SG10202100638XA (en) 2021-02-25
US20170014064A1 (en) 2017-01-19
CN104502579B (zh) 2018-04-13
HK1209185A1 (en) 2016-03-24
IL204877A (en) 2014-08-31
IL223602A (en) 2015-11-30
EP2205968A1 (fr) 2010-07-14
US9581588B2 (en) 2017-02-28
US20160266158A1 (en) 2016-09-15
JP2010540971A (ja) 2010-12-24
CA2701794A1 (fr) 2009-04-16
DK2657699T3 (en) 2017-07-10
CN108333379B (zh) 2021-09-07
US8822167B2 (en) 2014-09-02
IL223600A (en) 2015-08-31
NZ584963A (en) 2012-11-30
US9121851B2 (en) 2015-09-01
IL223600A0 (en) 2013-02-03
DK2205968T3 (en) 2014-02-17
KR101579327B1 (ko) 2015-12-21
US9588109B2 (en) 2017-03-07
JP2018151399A (ja) 2018-09-27
KR101844172B1 (ko) 2018-03-30
US20150377914A1 (en) 2015-12-31
US9285366B2 (en) 2016-03-15
US11143647B2 (en) 2021-10-12
IL223604B (en) 2018-07-31
US9012163B2 (en) 2015-04-21
EP4450163A2 (fr) 2024-10-23
US20220283150A1 (en) 2022-09-08
US11366106B2 (en) 2022-06-21
US8088593B2 (en) 2012-01-03

Similar Documents

Publication Publication Date Title
US11899010B2 (en) Modular point-of-care devices, systems, and uses thereof

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 20100429

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MT NL NO PL PT RO SE SI SK TR

AX Request for extension of the european patent

Extension state: AL BA MK RS

A4 Supplementary search report drawn up and despatched

Effective date: 20100831

RIC1 Information provided on ipc code assigned before grant

Ipc: G01N 33/48 20060101AFI20090506BHEP

Ipc: G01N 33/53 20060101ALI20100825BHEP

RIN1 Information on inventor provided before grant (corrected)

Inventor name: BURD, TAMMY

Inventor name: NUGENT, ANTHONY, JOSEPH

Inventor name: FRENZEL, GARY

Inventor name: HOLMES, ELIZABETH, A.

Inventor name: GIBBONS, IAN

DAX Request for extension of the european patent (deleted)
17Q First examination report despatched

Effective date: 20120103

RAP1 Party data changed (applicant data changed or rights of an application transferred)

Owner name: THERANOS, INC.

GRAP Despatch of communication of intention to grant a patent

Free format text: ORIGINAL CODE: EPIDOSNIGR1

INTG Intention to grant announced

Effective date: 20130507

RIN1 Information on inventor provided before grant (corrected)

Inventor name: BURD, TAMMY

Inventor name: GIBBONS, IAN

Inventor name: NUGENT, ANTHONY JOSEPH

Inventor name: FRENZEL, GARY

Inventor name: HOLMES, ELIZABETH A.

GRAS Grant fee paid

Free format text: ORIGINAL CODE: EPIDOSNIGR3

GRAA (expected) grant

Free format text: ORIGINAL CODE: 0009210

AK Designated contracting states

Kind code of ref document: B1

Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MT NL NO PL PT RO SE SI SK TR

REG Reference to a national code

Ref country code: GB

Ref legal event code: FG4D

REG Reference to a national code

Ref country code: CH

Ref legal event code: EP

REG Reference to a national code

Ref country code: AT

Ref legal event code: REF

Ref document number: 641933

Country of ref document: AT

Kind code of ref document: T

Effective date: 20131215

REG Reference to a national code

Ref country code: IE

Ref legal event code: FG4D

REG Reference to a national code

Ref country code: DE

Ref legal event code: R096

Ref document number: 602008028891

Country of ref document: DE

Effective date: 20140116

REG Reference to a national code

Ref country code: CH

Ref legal event code: NV

Representative=s name: MEYER AND KOLLEGEN, CH

REG Reference to a national code

Ref country code: DK

Ref legal event code: T3

Effective date: 20140213

REG Reference to a national code

Ref country code: NL

Ref legal event code: T3

REG Reference to a national code

Ref country code: SE

Ref legal event code: TRGR

REG Reference to a national code

Ref country code: ES

Ref legal event code: FG2A

Ref document number: 2447875

Country of ref document: ES

Kind code of ref document: T3

Effective date: 20140313

REG Reference to a national code

Ref country code: AT

Ref legal event code: MK05

Ref document number: 641933

Country of ref document: AT

Kind code of ref document: T

Effective date: 20131120

REG Reference to a national code

Ref country code: LT

Ref legal event code: MG4D

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: NO

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20140220

Ref country code: LT

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20131120

Ref country code: FI

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20131120

Ref country code: IS

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20140320

Ref country code: HR

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20131120

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: AT

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20131120

Ref country code: LV

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20131120

Ref country code: BE

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20131120

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: PT

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20140320

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: EE

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20131120

REG Reference to a national code

Ref country code: DE

Ref legal event code: R097

Ref document number: 602008028891

Country of ref document: DE

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: PL

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20131120

Ref country code: RO

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20131120

Ref country code: SK

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20131120

Ref country code: CZ

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20131120

PLBE No opposition filed within time limit

Free format text: ORIGINAL CODE: 0009261

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: NO OPPOSITION FILED WITHIN TIME LIMIT

26N No opposition filed

Effective date: 20140821

REG Reference to a national code

Ref country code: DE

Ref legal event code: R097

Ref document number: 602008028891

Country of ref document: DE

Effective date: 20140821

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: SI

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20131120

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: MC

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20131120

Ref country code: LU

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20141002

REG Reference to a national code

Ref country code: FR

Ref legal event code: PLFP

Year of fee payment: 8

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: BG

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20131120

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: GR

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20140221

Ref country code: CY

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20131120

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: HU

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT; INVALID AB INITIO

Effective date: 20081002

Ref country code: TR

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20131120

Ref country code: MT

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20131120

REG Reference to a national code

Ref country code: FR

Ref legal event code: PLFP

Year of fee payment: 9

REG Reference to a national code

Ref country code: FR

Ref legal event code: PLFP

Year of fee payment: 10

REG Reference to a national code

Ref country code: GB

Ref legal event code: 732E

Free format text: REGISTERED BETWEEN 20180315 AND 20180326

REG Reference to a national code

Ref country code: ES

Ref legal event code: PC2A

Owner name: THERANOS IP COMPANY, LLC

Effective date: 20180731

Ref country code: ES

Ref legal event code: PC2A

Effective date: 20180731

REG Reference to a national code

Ref country code: FR

Ref legal event code: PLFP

Year of fee payment: 11

REG Reference to a national code

Ref country code: DE

Ref legal event code: R082

Ref document number: 602008028891

Country of ref document: DE

Representative=s name: PATENTANWALTSKANZLEI MEYER, DE

Ref legal event code: R082

Ref document number: 602008028891

Country of ref document: DE

Ref country code: DE

Ref legal event code: R081

Ref document number: 602008028891

Country of ref document: DE

Owner name: LABRADOR DIAGNOSTICS LLC, WILMINGTON, US

Free format text: FORMER OWNER: THERANOS, INC., PALO ALTO, CALIF., US

Ref country code: DE

Ref legal event code: R081

Ref document number: 602008028891

Country of ref document: DE

Owner name: THERANOS IP COMPANY, LLC, NEWARK, US

Free format text: FORMER OWNER: THERANOS, INC., PALO ALTO, CALIF., US

REG Reference to a national code

Ref country code: DE

Ref legal event code: R082

Ref document number: 602008028891

Country of ref document: DE

Representative=s name: PATENTANWALTSKANZLEI MEYER, DE

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: SE

Payment date: 20191010

Year of fee payment: 12

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: DK

Payment date: 20191010

Year of fee payment: 12

REG Reference to a national code

Ref country code: CH

Ref legal event code: PUE

Owner name: LABRADOR DIAGNOSTICS LLC, US

Free format text: FORMER OWNER: THERANOS, INC., US

REG Reference to a national code

Ref country code: ES

Ref legal event code: PC2A

Owner name: LABRADOR DIAGNOSTICS LLC

Effective date: 20201123

REG Reference to a national code

Ref country code: DK

Ref legal event code: EBP

Effective date: 20201031

REG Reference to a national code

Ref country code: SE

Ref legal event code: EUG

REG Reference to a national code

Ref country code: NL

Ref legal event code: HC

Owner name: LABRADOR DIAGNOSTICS LLC; US

Free format text: DETAILS ASSIGNMENT: CHANGE OF OWNER(S), CHANGE OF OWNER(S) NAME; FORMER OWNER NAME: THERANOS IP COMPANY, LLC

Effective date: 20210503

Ref country code: NL

Ref legal event code: PD

Owner name: THERANOS IP COMPANY, LLC; US

Free format text: DETAILS ASSIGNMENT: CHANGE OF OWNER(S), ASSIGNMENT; FORMER OWNER NAME: THERANOS, INC.

Effective date: 20210503

REG Reference to a national code

Ref country code: DE

Ref legal event code: R082

Ref document number: 602008028891

Country of ref document: DE

Representative=s name: PATENTANWALTSKANZLEI MEYER, DE

Ref country code: DE

Ref legal event code: R081

Ref document number: 602008028891

Country of ref document: DE

Owner name: LABRADOR DIAGNOSTICS LLC, WILMINGTON, US

Free format text: FORMER OWNER: THERANOS IP COMPANY, LLC, NEWARK, CA, US

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: SE

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20201003

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: DK

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20201031

REG Reference to a national code

Ref country code: FR

Ref legal event code: PLFP

Year of fee payment: 15

P01 Opt-out of the competence of the unified patent court (upc) registered

Effective date: 20230516

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: NL

Payment date: 20230915

Year of fee payment: 16

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: ES

Payment date: 20231103

Year of fee payment: 16

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: CH

Payment date: 20231102

Year of fee payment: 16

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: IE

Payment date: 20240910

Year of fee payment: 17

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: GB

Payment date: 20240829

Year of fee payment: 17

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: FR

Payment date: 20240909

Year of fee payment: 17

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: IT

Payment date: 20240910

Year of fee payment: 17

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: DE

Payment date: 20240904

Year of fee payment: 17